Adenosine receptor signalling in Alzheimer's disease.


Journal

Purinergic signalling
ISSN: 1573-9546
Titre abrégé: Purinergic Signal
Pays: Netherlands
ID NLM: 101250499

Informations de publication

Date de publication:
09 2022
Historique:
received: 31 03 2022
accepted: 02 07 2022
pubmed: 24 7 2022
medline: 24 8 2022
entrez: 23 7 2022
Statut: ppublish

Résumé

Alzheimer's disease (AD) is the most common dementia in the elderly and its increasing prevalence presents treatment challenges. Despite a better understanding of the disease, the current mainstay of treatment cannot modify pathogenesis or effectively address the associated cognitive and memory deficits. Emerging evidence suggests adenosine G protein-coupled receptors (GPCRs) are promising therapeutic targets for Alzheimer's disease. The adenosine A

Identifiants

pubmed: 35870032
doi: 10.1007/s11302-022-09883-1
pii: 10.1007/s11302-022-09883-1
pmc: PMC9391555
doi:

Substances chimiques

Amyloid beta-Peptides 0
Receptors, Purinergic P1 0
Adenosine K72T3FS567

Types de publication

Journal Article Review Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

359-381

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2022. The Author(s).

Références

(2020) 2020 Alzheimer’s disease facts and figures. Alzheimer's Dement 16(3):391–460. https://doi.org/10.1002/alz.12068
Association AP (2013) Neurocognitive disorders. Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association Arlington, VA
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3):270–279. https://doi.org/10.1016/j.jalz.2011.03.008
doi: 10.1016/j.jalz.2011.03.008 pubmed: 21514249 pmcid: 3312027
Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, Van der Flier WM (2016) Alzheimer’s disease. Lancet 388(10043):505–517. https://doi.org/10.1016/s0140-6736(15)01124-1
doi: 10.1016/s0140-6736(15)01124-1 pubmed: 26921134
Brys M, Glodzik L, Mosconi L, Switalski R, De Santi S, Pirraglia E, Rich K, Kim BC, Mehta P, Zinkowski R, Pratico D, Wallin A, Zetterberg H, Tsui WH, Rusinek H, Blennow K, de Leon MJ (2009) Magnetic resonance imaging improves cerebrospinal fluid biomarkers in the early detection of Alzheimer’s disease. J Alzheimers Dis 16(2):351–362. https://doi.org/10.3233/JAD-2009-0968
doi: 10.3233/JAD-2009-0968 pubmed: 19221425 pmcid: 2754737
Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D, Gauthier S, Hampel H, Jicha GA, Meguro K, O’Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Sarazin M, de Souza LC, Stern Y, Visser PJ, Scheltens P (2010) Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 9(11):1118–1127. https://doi.org/10.1016/s1474-4422(10)70223-4
doi: 10.1016/s1474-4422(10)70223-4 pubmed: 20934914
Tapiola T, Alafuzoff I, Herukka SK, Parkkinen L, Hartikainen P, Soininen H, Pirttilä T (2009) Cerebrospinal fluid β-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol 66(3):382–389. https://doi.org/10.1001/archneurol.2008.596
doi: 10.1001/archneurol.2008.596 pubmed: 19273758
Fox NC, Scahill RI, Crum WR, Rossor MN (1999) Correlation between rates of brain atrophy and cognitive decline in AD. Neurology 52(8):1687–1689. https://doi.org/10.1212/wnl.52.8.1687
doi: 10.1212/wnl.52.8.1687 pubmed: 10331700
Jack CR Jr, Petersen RC, Xu YC, Waring SC, O’Brien PC, Tangalos EG, Smith GE, Ivnik RJ, Kokmen E (1997) Medial temporal atrophy on MRI in normal aging and very mild Alzheimer’s disease. Neurology 49(3):786–794. https://doi.org/10.1212/wnl.49.3.786
doi: 10.1212/wnl.49.3.786 pubmed: 9305341
Piguet O, Double KL, Kril JJ, Harasty J, Macdonald V, McRitchie DA, Halliday GM (2009) White matter loss in healthy ageing: a postmortem analysis. Neurobiol Aging 30(8):1288–1295. https://doi.org/10.1016/j.neurobiolaging.2007.10.015
doi: 10.1016/j.neurobiolaging.2007.10.015 pubmed: 18077060
Stout JC, Jernigan TL, Archibald SL, Salmon DP (1996) Association of dementia severity with cortical gray matter and abnormal white matter volumes in dementia of the Alzheimer type. Arch Neurol 53(8):742–749. https://doi.org/10.1001/archneur.1996.00550080056013
doi: 10.1001/archneur.1996.00550080056013 pubmed: 8759980
deToledo-Morrell L, Stoub TR, Bulgakova M, Wilson RS, Bennett DA, Leurgans S, Wuu J, Turner DA (2004) MRI-derived entorhinal volume is a good predictor of conversion from MCI to AD. Neurobiol Aging 25(9):1197–1203. https://doi.org/10.1016/j.neurobiolaging.2003.12.007
doi: 10.1016/j.neurobiolaging.2003.12.007 pubmed: 15312965
Dickerson BC, Stoub TR, Shah RC, Sperling RA, Killiany RJ, Albert MS, Hyman BT, Blacker D, Detoledo-Morrell L (2011) Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults. Neurol 76(16):1395–1402. https://doi.org/10.1212/WNL.0b013e3182166e96
doi: 10.1212/WNL.0b013e3182166e96
Du AT, Schuff N, Amend D, Laakso MP, Hsu YY, Jagust WJ, Yaffe K, Kramer JH, Reed B, Norman D, Chui HC, Weiner MW (2001) Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 71(4):441–447. https://doi.org/10.1136/jnnp.71.4.441
doi: 10.1136/jnnp.71.4.441 pubmed: 11561025
Jack CR Jr, Petersen RC, Xu YC, O’Brien PC, Smith GE, Ivnik RJ, Boeve BF, Waring SC, Tangalos EG, Kokmen E (1999) Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurol 52(7):1397–1403. https://doi.org/10.1212/wnl.52.7.1397
doi: 10.1212/wnl.52.7.1397
Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Sci 256(5054):184–185. https://doi.org/10.1126/science.1566067
doi: 10.1126/science.1566067
Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, Lieberburg I, Koo EH, Schenk D, Teplow DB et al (1992) Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nat 359(6393):322–325. https://doi.org/10.1038/359322a0
doi: 10.1038/359322a0
Bishop GM, Robinson SR (2004) Physiological roles of amyloid-beta and implications for its removal in Alzheimer’s disease. Drugs Aging 21(10):621–630. https://doi.org/10.2165/00002512-200421100-00001
doi: 10.2165/00002512-200421100-00001 pubmed: 15287821
Grimm MO, Grimm HS, Hartmann T (2007) Amyloid beta as a regulator of lipid homeostasis. Trends Mol Med 13(8):337–344. https://doi.org/10.1016/j.molmed.2007.06.004
doi: 10.1016/j.molmed.2007.06.004 pubmed: 17644432
Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y (1994) Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron 13(1):45–53. https://doi.org/10.1016/0896-6273(94)90458-8
doi: 10.1016/0896-6273(94)90458-8 pubmed: 8043280
Miller DL, Papayannopoulos IA, Styles J, Bobin SA, Lin YY, Biemann K, Iqbal K (1993) Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer’s disease. Arch Biochem Biophys 301(1):41–52. https://doi.org/10.1006/abbi.1993.1112
doi: 10.1006/abbi.1993.1112 pubmed: 8442665
Beyreuther K, Masters CL (1991) Amyloid precursor protein (APP) and beta A4 amyloid in the etiology of Alzheimer’s disease: precursor-product relationships in the derangement of neuronal function. Brain Pathol 1(4):241–251. https://doi.org/10.1111/j.1750-3639.1991.tb00667.x
doi: 10.1111/j.1750-3639.1991.tb00667.x pubmed: 1669714
Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12(10):383–388. https://doi.org/10.1016/0165-6147(91)90609-v
doi: 10.1016/0165-6147(91)90609-v pubmed: 1763432
Selkoe DJ (1991) The molecular pathology of Alzheimer’s disease. Neuron 6(4):487–498. https://doi.org/10.1016/0896-6273(91)90052-2
doi: 10.1016/0896-6273(91)90052-2 pubmed: 1673054
Caceres A, Kosik KS (1990) Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons. Nature 343(6257):461–463. https://doi.org/10.1038/343461a0
doi: 10.1038/343461a0 pubmed: 2105469
Drubin DG, Kirschner MW (1986) Tau protein function in living cells. J Cell Biol 103(6 Pt 2):2739–2746. https://doi.org/10.1083/jcb.103.6.2739
doi: 10.1083/jcb.103.6.2739 pubmed: 3098742
Lace GL, Wharton SB, Ince PG (2007) A brief history of tau: the evolving view of the microtubule-associated protein tau in neurodegenerative diseases. Clin Neuropathol 26(2):43–58. https://doi.org/10.5414/npp26043
doi: 10.5414/npp26043 pubmed: 17416103
Alvarez A, Toro R, Cáceres A, Maccioni RB (1999) Inhibition of tau phosphorylating protein kinase cdk5 prevents beta-amyloid-induced neuronal death. FEBS Lett 459(3):421–426. https://doi.org/10.1016/s0014-5793(99)01279-x
doi: 10.1016/s0014-5793(99)01279-x pubmed: 10526177
Lee G, Thangavel R, Sharma VM, Litersky JM, Bhaskar K, Fang SM, Do LH, Andreadis A, Van Hoesen G, Ksiezak-Reding H (2004) Phosphorylation of tau by fyn: implications for Alzheimer’s disease. J Neurosci 24(9):2304–2312. https://doi.org/10.1523/jneurosci.4162-03.2004
doi: 10.1523/jneurosci.4162-03.2004 pubmed: 14999081 pmcid: 6730442
Lindwall G, Cole RD (1984) Phosphorylation affects the ability of tau protein to promote microtubule assembly. J Biol Chem 259(8):5301–5305
doi: 10.1016/S0021-9258(17)42989-9 pubmed: 6425287
Lucas JJ, Hernández F, Gómez-Ramos P, Morán MA, Hen R, Avila J (2001) Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. Embo j 20(1–2):27–39. https://doi.org/10.1093/emboj/20.1.27
doi: 10.1093/emboj/20.1.27 pubmed: 11226152 pmcid: 140191
Rickle A, Bogdanovic N, Volkman I, Winblad B, Ravid R, Cowburn RF (2004) Akt activity in Alzheimer’s disease and other neurodegenerative disorders. NeuroReport 15(6):955–959. https://doi.org/10.1097/00001756-200404290-00005
doi: 10.1097/00001756-200404290-00005 pubmed: 15076714
Hensley K, Floyd RA, Zheng NY, Nael R, Robinson KA, Nguyen X, Pye QN, Stewart CA, Geddes J, Markesbery WR, Patel E, Johnson GV, Bing G (1999) p38 kinase is activated in the Alzheimer’s disease brain. J Neurochem 72(5):2053–2058. https://doi.org/10.1046/j.1471-4159.1999.0722053.x
doi: 10.1046/j.1471-4159.1999.0722053.x pubmed: 10217284
Zhu X, Castellani RJ, Takeda A, Nunomura A, Atwood CS, Perry G, Smith MA (2001) Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: the ‘two hit’ hypothesis. Mech Ageing Dev 123(1):39–46. https://doi.org/10.1016/s0047-6374(01)00342-6
doi: 10.1016/s0047-6374(01)00342-6 pubmed: 11640950
Alonso AC, Zaidi T, Grundke-Iqbal I, Iqbal K (1994) Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease. Proc Natl Acad Sci USA 91(12):5562–5566. https://doi.org/10.1073/pnas.91.12.5562
doi: 10.1073/pnas.91.12.5562 pubmed: 8202528 pmcid: 44036
Ruben GC, Iqbal K, Wisniewski HM, Johnson JE Jr, Grundke-Iqbal I (1993) Alzheimer neurofibrillary tangles contain 2.1 nm filaments structurally identical to the microtubule-associated protein tau: a high-resolution transmission electron microscope study of tangles and senile plaque core amyloid. Brain Res 602(2):164–179. https://doi.org/10.1016/0006-8993(92)91092-s
doi: 10.1016/0006-8993(92)91092-s pubmed: 7680597
Braak H, Braak E, Grundke-Iqbal I, Iqbal K (1986) Occurrence of neuropil threads in the senile human brain and in Alzheimer’s disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett 65(3):351–355. https://doi.org/10.1016/0304-3940(86)90288-0
doi: 10.1016/0304-3940(86)90288-0 pubmed: 2423928
Cras P, Kawai M, Siedlak S, Perry G (1991) Microglia are associated with the extracellular neurofibrillary tangles of Alzheimer disease. Brain Res 558(2):312–314. https://doi.org/10.1016/0006-8993(91)90783-r
doi: 10.1016/0006-8993(91)90783-r pubmed: 1782548
Goedert M, Spillantini MG, Jakes R, Crowther RA, Vanmechelen E, Probst A, Götz J, Bürki K, Cohen P (1995) Molecular dissection of the paired helical filament. Neurobiol Aging 16(3):325–334. https://doi.org/10.1016/0197-4580(95)00017-9
doi: 10.1016/0197-4580(95)00017-9 pubmed: 7566342
Probst A, Ulrich J, Heitz PU (1982) Senile dementia of Alzheimer type: astroglial reaction to extracellular neurofibrillary tangles in the hippocampus. An immunocytochemical and electron-microscopic study. Acta Neuropathol 57(1):75–79. https://doi.org/10.1007/bf00688880
doi: 10.1007/bf00688880 pubmed: 7090745
Goedert M, Spillantini MG (2006) A century of Alzheimer’s disease. Sci 314(5800):777–781. https://doi.org/10.1126/science.1132814
doi: 10.1126/science.1132814
Bennett DA, Schneider JA, Wilson RS, Bienias JL, Arnold SE (2004) Neurofibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function. Arch Neurol 61(3):378–384. https://doi.org/10.1001/archneur.61.3.378
doi: 10.1001/archneur.61.3.378 pubmed: 15023815
Gómez-Isla T, Hollister R, West H, Mui S, Growdon JH, Petersen RC, Parisi JE, Hyman BT (1997) Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer’s disease. Ann Neurol 41(1):17–24. https://doi.org/10.1002/ana.410410106
doi: 10.1002/ana.410410106 pubmed: 9005861
Braak H, Braak E (1997) Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 18(4):351–357. https://doi.org/10.1016/s0197-4580(97)00056-0
doi: 10.1016/s0197-4580(97)00056-0 pubmed: 9330961
Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, Smith GE, Dickson DW, Johnson KA, Petersen LE, McDonald WC, Braak H, Petersen RC (2003) Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol 62(11):1087–1095. https://doi.org/10.1093/jnen/62.11.1087
doi: 10.1093/jnen/62.11.1087 pubmed: 14656067
Price JL, Morris JC (1999) Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 45(3):358–368. https://doi.org/10.1002/1531-8249(199903)45:3%3c358::aid-ana12%3e3.0.co;2-x
doi: 10.1002/1531-8249(199903)45:3<358::aid-ana12>3.0.co;2-x pubmed: 10072051
Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C (2009) Age, neuropathology, and dementia. N Engl J Med 360(22):2302–2309. https://doi.org/10.1056/NEJMoa0806142
doi: 10.1056/NEJMoa0806142 pubmed: 19474427
Boutajangout A, Ingadottir J, Davies P, Sigurdsson EM (2011) Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brain. J Neurochem 118(4):658–667. https://doi.org/10.1111/j.1471-4159.2011.07337.x
doi: 10.1111/j.1471-4159.2011.07337.x pubmed: 21644996 pmcid: 3366469
Boutajangout A, Wisniewski T (2014) Tau-based therapeutic approaches for Alzheimer’s disease - a mini-review. Gerontology 60(5):381–385. https://doi.org/10.1159/000358875
doi: 10.1159/000358875 pubmed: 24732638
McGeer PL, McGeer EG (2013) The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol 126(4):479–497. https://doi.org/10.1007/s00401-013-1177-7
doi: 10.1007/s00401-013-1177-7 pubmed: 24052108
Brosseron F, Krauthausen M, Kummer M, Heneka MT (2014) Body fluid cytokine levels in mild cognitive impairment and Alzheimer’s disease: a comparative overview. Mol Neurobiol 50(2):534–544. https://doi.org/10.1007/s12035-014-8657-1
doi: 10.1007/s12035-014-8657-1 pubmed: 24567119 pmcid: 4182618
Tarkowski E, Andreasen N, Tarkowski A, Blennow K (2003) Intrathecal inflammation precedes development of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 74(9):1200–1205. https://doi.org/10.1136/jnnp.74.9.1200
doi: 10.1136/jnnp.74.9.1200 pubmed: 12933918 pmcid: 1738668
Benzing WC, Wujek JR, Ward EK, Shaffer D, Ashe KH, Younkin SG, Brunden KR (1999) Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice. Neurobiol Aging 20(6):581–589. https://doi.org/10.1016/s0197-4580(99)00065-2
doi: 10.1016/s0197-4580(99)00065-2 pubmed: 10674423
Castellani RJ, Lee HG, Zhu X, Perry G, Smith MA (2008) Alzheimer disease pathology as a host response. J Neuropathol Exp Neurol 67(6):523–531. https://doi.org/10.1097/NEN.0b013e318177eaf4
doi: 10.1097/NEN.0b013e318177eaf4 pubmed: 18520771
Graeber MB, Streit WJ (2010) Microglia: biology and pathology. Acta Neuropathol 119(1):89–105. https://doi.org/10.1007/s00401-009-0622-0
doi: 10.1007/s00401-009-0622-0 pubmed: 20012873
Heppner FL, Ransohoff RM, Becher B (2015) Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci 16(6):358–372. https://doi.org/10.1038/nrn3880
doi: 10.1038/nrn3880 pubmed: 25991443
Wyss-Coray T, Mucke L (2002) Inflammation in neurodegenerative disease–a double-edged sword. Neuron 35(3):419–432. https://doi.org/10.1016/s0896-6273(02)00794-8
doi: 10.1016/s0896-6273(02)00794-8 pubmed: 12165466
Koistinaho M, Lin S, Wu X, Esterman M, Koger D, Hanson J, Higgs R, Liu F, Malkani S, Bales KR, Paul SM (2004) Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides. Nat Med 10(7):719–726. https://doi.org/10.1038/nm1058
doi: 10.1038/nm1058 pubmed: 15195085
Simard AR, Soulet D, Gowing G, Julien JP, Rivest S (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 49(4):489–502. https://doi.org/10.1016/j.neuron.2006.01.022
doi: 10.1016/j.neuron.2006.01.022 pubmed: 16476660
Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O’Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21(3):383–421. https://doi.org/10.1016/s0197-4580(00)00124-x
doi: 10.1016/s0197-4580(00)00124-x pubmed: 10858586 pmcid: 3887148
Hickman SE, Allison EK, El Khoury J (2008) Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J Neurosci 28(33):8354–8360. https://doi.org/10.1523/jneurosci.0616-08.2008
doi: 10.1523/jneurosci.0616-08.2008 pubmed: 18701698 pmcid: 2597474
Jimenez S, Baglietto-Vargas D, Caballero C, Moreno-Gonzalez I, Torres M, Sanchez-Varo R, Ruano D, Vizuete M, Gutierrez A, Vitorica J (2008) Inflammatory response in the hippocampus of PS1M146L/APP751SL mouse model of Alzheimer’s disease: age-dependent switch in the microglial phenotype from alternative to classic. J Neurosci 28(45):11650–11661. https://doi.org/10.1523/jneurosci.3024-08.2008
doi: 10.1523/jneurosci.3024-08.2008 pubmed: 18987201 pmcid: 6671312
Chiang K, Koo EH (2014) Emerging therapeutics for Alzheimer’s disease. Annu Rev Pharmacol Toxicol 54:381–405. https://doi.org/10.1146/annurev-pharmtox-011613-135932
doi: 10.1146/annurev-pharmtox-011613-135932 pubmed: 24392696
Wyss-Coray T, Rogers J (2012) Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb Perspect Med 2(1):a006346–a006346. https://doi.org/10.1101/cshperspect.a006346
doi: 10.1101/cshperspect.a006346 pubmed: 22315714 pmcid: 3253025
Graeber MB, Christie MJ (2012) Multiple mechanisms of microglia: a gatekeeper’s contribution to pain states. Exp Neurol 234(2):255–261. https://doi.org/10.1016/j.expneurol.2012.01.007
doi: 10.1016/j.expneurol.2012.01.007 pubmed: 22273537
Henkel JS, Beers DR, Zhao W, Appel SH (2009) Microglia in ALS: the good, the bad, and the resting. J Neuroimmune Pharmacol 4(4):389–398. https://doi.org/10.1007/s11481-009-9171-5
doi: 10.1007/s11481-009-9171-5 pubmed: 19731042
Ji K, Akgul G, Wollmuth LP, Tsirka SE (2013) Microglia actively regulate the number of functional synapses. PLoS ONE 8(2):e56293. https://doi.org/10.1371/journal.pone.0056293
doi: 10.1371/journal.pone.0056293 pubmed: 23393609 pmcid: 3564799
Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Sci 308(5726):1314–1318. https://doi.org/10.1126/science.1110647
doi: 10.1126/science.1110647
Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119(1):7–35. https://doi.org/10.1007/s00401-009-0619-8
doi: 10.1007/s00401-009-0619-8 pubmed: 20012068
Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4(3):229–237. https://doi.org/10.1111/j.1750-3639.1994.tb00838.x
doi: 10.1111/j.1750-3639.1994.tb00838.x pubmed: 7952264
London A, Cohen M, Schwartz M (2013) Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair. Front Cell Neurosci 7:34. https://doi.org/10.3389/fncel.2013.00034
doi: 10.3389/fncel.2013.00034 pubmed: 23596391 pmcid: 3625831
Abramov AY, Canevari L, Duchen MR (2003) Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity. J Neurosci 23(12):5088–5095. https://doi.org/10.1523/jneurosci.23-12-05088.2003
doi: 10.1523/jneurosci.23-12-05088.2003 pubmed: 12832532 pmcid: 6741151
Blasko I, Veerhuis R, Stampfer-Kountchev M, Saurwein-Teissl M, Eikelenboom P, Grubeck-Loebenstein B (2000) Costimulatory effects of interferon-gamma and interleukin-1beta or tumor necrosis factor alpha on the synthesis of Abeta1–40 and Abeta1–42 by human astrocytes. Neurobiol Dis 7(6 Pt B):682–689. https://doi.org/10.1006/nbdi.2000.0321
doi: 10.1006/nbdi.2000.0321 pubmed: 11114266
Fuller S, Steele M, Münch G (2010) Activated astroglia during chronic inflammation in Alzheimer’s disease–do they neglect their neurosupportive roles? Mutat Res 690(1–2):40–49. https://doi.org/10.1016/j.mrfmmm.2009.08.016
doi: 10.1016/j.mrfmmm.2009.08.016 pubmed: 19748514
Oberstein TJ, Spitzer P, Klafki HW, Linning P, Neff F, Knölker HJ, Lewczuk P, Wiltfang J, Kornhuber J, Maler JM (2015) Astrocytes and microglia but not neurons preferentially generate N-terminally truncated Aβ peptides. Neurobiol Dis 73:24–35. https://doi.org/10.1016/j.nbd.2014.08.031
doi: 10.1016/j.nbd.2014.08.031 pubmed: 25204716
Sudduth TL, Schmitt FA, Nelson PT, Wilcock DM (2013) Neuroinflammatory phenotype in early Alzheimer’s disease. Neurobiol Aging 34(4):1051–1059. https://doi.org/10.1016/j.neurobiolaging.2012.09.012
doi: 10.1016/j.neurobiolaging.2012.09.012 pubmed: 23062700
Kuruppu S, Rajapakse NW, Parkington HC, Smith AI (2017) The characteristics of astrocyte on Aβ clearance altered in Alzheimer’s disease were reversed by anti-inflammatory agent (+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate. Am J Transl Res 9(7):3514–3516
pubmed: 28804567 pmcid: 5553888
Söllvander S, Nikitidou E, Brolin R, Söderberg L, Sehlin D, Lannfelt L, Erlandsson A (2016) Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons. Mol Neurodegener 11(1):38. https://doi.org/10.1186/s13024-016-0098-z
doi: 10.1186/s13024-016-0098-z pubmed: 27176225 pmcid: 4865996
Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White CL 3rd, Araoz C (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 86(19):7611–7615. https://doi.org/10.1073/pnas.86.19.7611
doi: 10.1073/pnas.86.19.7611 pubmed: 2529544 pmcid: 298116
Fillit H, Ding WH, Buee L, Kalman J, Altstiel L, Lawlor B, Wolf-Klein G (1991) Elevated circulating tumor necrosis factor levels in Alzheimer’s disease. Neurosci Lett 129(2):318–320. https://doi.org/10.1016/0304-3940(91)90490-k
doi: 10.1016/0304-3940(91)90490-k pubmed: 1745413
Hoffmann A, Kann O, Ohlemeyer C, Hanisch UK, Kettenmann H (2003) Elevation of basal intracellular calcium as a central element in the activation of brain macrophages (microglia): suppression of receptor-evoked calcium signaling and control of release function. J Neurosci 23(11):4410–4419
doi: 10.1523/JNEUROSCI.23-11-04410.2003 pubmed: 12805281 pmcid: 6740788
Reed-Geaghan EG, Savage JC, Hise AG, Landreth GE (2009) CD14 and toll-like receptors 2 and 4 are required for fibrillar A{beta}-stimulated microglial activation. J Neurosci 29(38):11982–11992. https://doi.org/10.1523/jneurosci.3158-09.2009
doi: 10.1523/jneurosci.3158-09.2009 pubmed: 19776284 pmcid: 2778845
Toescu EC, Möller T, Kettenmann H, Verkhratsky A (1998) Long-term activation of capacitative Ca2+ entry in mouse microglial cells. Neuroscience 86(3):925–935. https://doi.org/10.1016/S0306-4522(98)00123-7
doi: 10.1016/S0306-4522(98)00123-7 pubmed: 9692728
Vom Berg J, Prokop S, Miller KR, Obst J, Kälin RE, Lopategui-Cabezas I, Wegner A, Mair F, Schipke CG, Peters O, Winter Y, Becher B, Heppner FL (2012) Inhibition of IL-12/IL-23 signaling reduces Alzheimer’s disease-like pathology and cognitive decline. Nat Med 18(12):1812–1819. https://doi.org/10.1038/nm.2965
doi: 10.1038/nm.2965
Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, Yarasheski KE, Bateman RJ (2010) Decreased clearance of CNS beta-amyloid in Alzheimer’s disease. Science 330(6012):1774. https://doi.org/10.1126/science.1197623
doi: 10.1126/science.1197623 pubmed: 21148344 pmcid: 3073454
Stalder M, Deller T, Staufenbiel M, Jucker M (2001) 3D-Reconstruction of microglia and amyloid in APP23 transgenic mice: no evidence of intracellular amyloid. Neurobiol Aging 22(3):427–434. https://doi.org/10.1016/s0197-4580(01)00209-3
doi: 10.1016/s0197-4580(01)00209-3 pubmed: 11378249
Wegiel J, Wang KC, Imaki H, Rubenstein R, Wronska A, Osuchowski M, Lipinski WJ, Walker LC, LeVine H (2001) The role of microglial cells and astrocytes in fibrillar plaque evolution in transgenic APP(SW) mice. Neurobiol Aging 22(1):49–61. https://doi.org/10.1016/s0197-4580(00)00181-0
doi: 10.1016/s0197-4580(00)00181-0 pubmed: 11164276
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541(7638):481–487. https://doi.org/10.1038/nature21029
doi: 10.1038/nature21029 pubmed: 28099414 pmcid: 5404890
Hamby ME, Coppola G, Ao Y, Geschwind DH, Khakh BS, Sofroniew MV (2012) Inflammatory mediators alter the astrocyte transcriptome and calcium signaling elicited by multiple G-protein-coupled receptors. J Neurosci 32(42):14489. https://doi.org/10.1523/JNEUROSCI.1256-12.2012
doi: 10.1523/JNEUROSCI.1256-12.2012 pubmed: 23077035 pmcid: 3518872
Haque ME, Kim I-S, Jakaria M, Akther M, Choi D-K (2018) Importance of GPCR-mediated microglial activation in Alzheimer’s disease. Front Cell Neurosci 12:258–258. https://doi.org/10.3389/fncel.2018.00258
doi: 10.3389/fncel.2018.00258 pubmed: 30186116 pmcid: 6110855
Zhang F, Zhong R-j, Cheng C, Li S, Le W-d (2020) New therapeutics beyond amyloid-β and tau for the treatment of Alzheimer’s disease. Acta Pharmacologica Sinica. https://doi.org/10.1038/s41401-020-00565-5
doi: 10.1038/s41401-020-00565-5 pubmed: 33318625 pmcid: 8463684
Cummings J, Lee G, Zhong K, Fonseca J, Taghva K (2021) Alzheimer’s disease drug development pipeline: 2021. Alzheimers Dement (N Y) 7(1):e12179. https://doi.org/10.1002/trc2.12179
doi: 10.1002/trc2.12179
van Bokhoven P, de Wilde A, Vermunt L, Leferink PS, Heetveld S, Cummings J, Scheltens P, Vijverberg EGB (2021) The Alzheimer’s disease drug development landscape. Alzheimers Res Ther 13(1):186. https://doi.org/10.1186/s13195-021-00927-z
doi: 10.1186/s13195-021-00927-z pubmed: 34763720 pmcid: 8582156
Haeberlein SB, Salloway S, Aisen P, Frederik B, Castrillo-Viguera C, Chen T, Cohen S, Hansson O, He P, Iwatsubo T, Mallinkrodt C, Mummery CJ, Muralidharan KK, Nisenbaum L, Rajagovindan R, Vellas B, Wu S, Yang L, Tian Y (2021) Evaluation of aducanumab efficacy in early Alzheimer’s disease. Paper presented at: 15th International Conference on Alzheimer's & Parkinson's Diseases virtual conference; March 9–14, 2021
Cummings J, Aisen P, Lemere C, Atri A, Sabbagh M, Salloway S (2021) Aducanumab produced a clinically meaningful benefit in association with amyloid lowering. Alzheimers Res Ther 13(1):98. https://doi.org/10.1186/s13195-021-00838-z
doi: 10.1186/s13195-021-00838-z pubmed: 33971962 pmcid: 8111757
Knopman DS, Jones DT (2019) Greicius MD (2021) Failure to demonstrate efficacy of aducanumab: an analysis of the EMERGE and ENGAGE trials as reported by Biogen. Alzheimers Dement 17(4):696–701. https://doi.org/10.1002/alz.12213
doi: 10.1002/alz.12213
Tampi RR, Forester BP, Agronin M (2021) Aducanumab: evidence from clinical trial data and controversies. Drugs Context 10. https://doi.org/10.7573/dic.2021-7-3
Klein G, Delmar P, Voyle N, Rehal S, Hofmann C, Abi-Saab D, Andjelkovic M, Ristic S, Wang G, Bateman R, Kerchner GA, Baudler M, Fontoura P, Doody R (2019) Gantenerumab reduces amyloid-beta plaques in patients with prodromal to moderate Alzheimer’s disease: a PET substudy interim analysis. Alzheimer’s res ther 11(1):101. https://doi.org/10.1186/s13195-019-0559-z
doi: 10.1186/s13195-019-0559-z
Mintun MA, Lo AC, Duggan Evans C, Wessels AM, Ardayfio PA, Andersen SW, Shcherbinin S, Sparks J, Sims JR, Brys M, Apostolova LG, Salloway SP, Skovronsky DM (2021) Donanemab in early Alzheimer’s disease. N Engl J Med 384(18):1691–1704. https://doi.org/10.1056/NEJMoa2100708
doi: 10.1056/NEJMoa2100708 pubmed: 33720637
Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, Lannfelt L, Bradley H, Rabe M, Koyama A, Reyderman L, Berry DA, Berry S, Gordon R, Kramer LD, Cummings JL (2021) A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Abeta protofibril antibody. Alzheimers Res Ther 13(1):80. https://doi.org/10.1186/s13195-021-00813-8
doi: 10.1186/s13195-021-00813-8 pubmed: 33865446 pmcid: 8053280
Doody RS, Farlow M, Aisen PS (2014) Phase 3 trials of solanezumab and bapineuzumab for Alzheimer’s disease. N Engl J Med 370(15):1460. https://doi.org/10.1056/NEJMc1402193
doi: 10.1056/NEJMc1402193 pubmed: 24716687
Doody RS, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, He F, Sun X, Thomas RG, Aisen PS, Siemers E, Sethuraman G, Mohs R (2013) A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N Engl J Med 369(4):341–350. https://doi.org/10.1056/NEJMoa1210951
doi: 10.1056/NEJMoa1210951 pubmed: 23883379
Galasko D, Bell J, Mancuso JY, Kupiec JW, Sabbagh MN, van Dyck C, Thomas RG, Aisen PS (2014) Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease. Neurol 82(17):1536–1542. https://doi.org/10.1212/wnl.0000000000000364
doi: 10.1212/wnl.0000000000000364
Gauthier S, Feldman HH, Schneider LS, Wilcock GK, Frisoni GB, Hardlund JH, Moebius HJ, Bentham P, Kook KA, Wischik DJ, Schelter BO, Davis CS, Staff RT, Bracoud L, Shamsi K, Storey JM, Harrington CR, Wischik CM (2016) Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer’s disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 388(10062):2873–2884. https://doi.org/10.1016/s0140-6736(16)31275-2
doi: 10.1016/s0140-6736(16)31275-2 pubmed: 27863809 pmcid: 5164296
Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M, Ketter N, Nejadnik B, Guenzler V, Miloslavsky M, Wang D, Lu Y, Lull J, Tudor IC, Liu E, Grundman M, Yuen E, Black R, Brashear HR (2014) Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med 370(4):322–333. https://doi.org/10.1056/NEJMoa1304839
doi: 10.1056/NEJMoa1304839 pubmed: 24450891 pmcid: 4159618
Vandenberghe R, Rinne JO, Boada M, Katayama S, Scheltens P, Vellas B, Tuchman M, Gass A, Fiebach JB, Hill D, Lobello K, Li D, McRae T, Lucas P, Evans I, Booth K, Luscan G, Wyman BT, Hua L, Yang L, Brashear HR, Black RS (2016) Bapineuzumab for mild to moderate Alzheimer’s disease in two global, randomized, phase 3 trials. Alzheimers Res Ther 8(1):18. https://doi.org/10.1186/s13195-016-0189-7
doi: 10.1186/s13195-016-0189-7 pubmed: 27176461 pmcid: 4866415
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261(5123):921–923
doi: 10.1126/science.8346443 pubmed: 8346443
McGeer PL, Schulzer M, McGeer EG (1996) Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology 47(2):425–432. https://doi.org/10.1212/wnl.47.2.425
doi: 10.1212/wnl.47.2.425 pubmed: 8757015
Stewart WF, Kawas C, Corrada M, Metter EJ (1997) Risk of Alzheimer’s disease and duration of NSAID use. Neurology 48(3):626–632. https://doi.org/10.1212/wnl.48.3.626
doi: 10.1212/wnl.48.3.626 pubmed: 9065537
Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90(5):1977–1981
doi: 10.1073/pnas.90.5.1977 pubmed: 8446617 pmcid: 46003
Vlad SC, Miller DR, Kowall NW, Felson DT (2008) Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 70(19):1672–1677. https://doi.org/10.1212/01.wnl.0000311269.57716.63
doi: 10.1212/01.wnl.0000311269.57716.63 pubmed: 18458226
Zannis VI, Breslow JL, Utermann G, Mahley RW, Weisgraber KH, Havel RJ, Goldstein JL, Brown MS, Schonfeld G, Hazzard WR, Blum C (1982) Proposed nomenclature of apoE isoproteins, apoE genotypes, and phenotypes. J Lipid Res 23(6):911–914
doi: 10.1016/S0022-2275(20)38094-9 pubmed: 7130859
Aisen PS (2002) Evaluation of selective COX-2 inhibitors for the treatment of Alzheimer’s disease. J Pain Symptom Manage 23(4 Suppl):S35-40. https://doi.org/10.1016/s0885-3924(02)00374-3
doi: 10.1016/s0885-3924(02)00374-3 pubmed: 11992749
Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ (2003) Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 289(21):2819–2826. https://doi.org/10.1001/jama.289.21.2819
doi: 10.1001/jama.289.21.2819 pubmed: 12783912
Martin BK, Szekely C, Brandt J, Piantadosi S, Breitner JC, Craft S, Evans D, Green R, Mullan M (2008) Cognitive function over time in the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib. Arch Neurol 65(7):896–905. https://doi.org/10.1001/archneur.2008.65.7.nct70006
doi: 10.1001/archneur.2008.65.7.nct70006 pubmed: 18474729
Breitner JC, Baker LD, Montine TJ, Meinert CL, Lyketsos CG, Ashe KH, Brandt J, Craft S, Evans DE, Green RC, Ismail MS, Martin BK, Mullan MJ, Sabbagh M, Tariot PN (2011) Extended results of the Alzheimer’s disease anti-inflammatory prevention trial. Alzheimers Dement 7(4):402–411. https://doi.org/10.1016/j.jalz.2010.12.014
doi: 10.1016/j.jalz.2010.12.014 pubmed: 21784351 pmcid: 3149804
Dal Pra I, Armato U, Chiarini A (2019) Family C G-protein-coupled receptors in Alzheimer’s disease and therapeutic implications. Front Pharmacol 10:1282. https://doi.org/10.3389/fphar.2019.01282
doi: 10.3389/fphar.2019.01282
Thathiah A, De Strooper B (2011) The role of G protein-coupled receptors in the pathology of Alzheimer’s disease. Nat Rev Neurosci 12(2):73–87. https://doi.org/10.1038/nrn2977
doi: 10.1038/nrn2977 pubmed: 21248787
Zhao J, Deng Y, Jiang Z, Qing H (2016) G Protein-Coupled Receptors (GPCRs) in Alzheimer’s disease: a focus on BACE1 related GPCRs. Front Aging Neurosci 8:58. https://doi.org/10.3389/fnagi.2016.00058
doi: 10.3389/fnagi.2016.00058 pubmed: 27047374 pmcid: 4805599
Rosenbaum DM, Rasmussen SG, Kobilka BK (2009) The structure and function of G-protein-coupled receptors. Nature 459(7245):356–363. https://doi.org/10.1038/nature08144
doi: 10.1038/nature08144 pubmed: 19458711 pmcid: 3967846
Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW (2004) Incipient Alzheimer’s disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci USA 101(7):2173
doi: 10.1073/pnas.0308512100 pubmed: 14769913 pmcid: 357071
Cortellis (2022) Cortellis Drug Discovery Intelligence. https://www.cortelliscom/intelligence/homedo Accessed 17 March 2022
Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR, Shippy D, Tan J (2006) Caffeine protects Alzheimer’s mice against cognitive impairment and reduces brain beta-amyloid production. Neuroscience 142(4):941–952. https://doi.org/10.1016/j.neuroscience.2006.07.021
doi: 10.1016/j.neuroscience.2006.07.021 pubmed: 16938404
Giunta S, Andriolo V, Castorina A (2014) Dual blockade of the A1 and A2A adenosine receptor prevents amyloid beta toxicity in neuroblastoma cells exposed to aluminum chloride. Int J Biochem Cell Biol 54:122–136. https://doi.org/10.1016/j.biocel.2014.07.009
doi: 10.1016/j.biocel.2014.07.009 pubmed: 25058312
Fredholm BB, Arslan G, Halldner L, Kull B, Schulte G, Wasserman W (2000) Structure and function of adenosine receptors and their genes. Naunyn Schmiedebergs Arch Pharmacol 362(4–5):364–374
doi: 10.1007/s002100000313 pubmed: 11111830
Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55. https://doi.org/10.1146/annurev.neuro.24.1.31
doi: 10.1146/annurev.neuro.24.1.31 pubmed: 11283304
Costenla AR, Cunha RA, de Mendonça A (2010) Caffeine, adenosine receptors, and synaptic plasticity. J Alzheimers Dis 20(Suppl 1):S25-34. https://doi.org/10.3233/jad-2010-091384
doi: 10.3233/jad-2010-091384 pubmed: 20182030
Costenla AR, Diógenes MJ, Canas PM, Rodrigues RJ, Nogueira C, Maroco J, Agostinho PM, Ribeiro JA, Cunha RA, de Mendonça A (2011) Enhanced role of adenosine A(2A) receptors in the modulation of LTP in the rat hippocampus upon ageing. Eur J Neurosci 34(1):12–21. https://doi.org/10.1111/j.1460-9568.2011.07719.x
doi: 10.1111/j.1460-9568.2011.07719.x pubmed: 21615561
Fredholm BB, Ijzerman AP, Jacobson KA, Klotz K-N, Linden J (2001) International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors. Pharmacol Rev 53(4):527
pubmed: 11734617
Rivkees SA, Price SL, Zhou FC (1995) Immunohistochemical detection of A1 adenosine receptors in rat brain with emphasis on localization in the hippocampal formation, cerebral cortex, cerebellum, and basal ganglia. Brain Res 677(2):193–203. https://doi.org/10.1016/0006-8993(95)00062-u
doi: 10.1016/0006-8993(95)00062-u pubmed: 7552243
Schindler M, Harris CA, Hayes B, Papotti M, Humphrey PP (2001) Immunohistochemical localization of adenosine A1 receptors in human brain regions. Neurosci Lett 297(3):211–215. https://doi.org/10.1016/s0304-3940(00)01643-8
doi: 10.1016/s0304-3940(00)01643-8 pubmed: 11137765
Ochiishi T, Saitoh Y, Yukawa A, Saji M, Ren Y, Shirao T, Miyamoto H, Nakata H, Sekino Y (1999) High level of adenosine A1 receptor-like immunoreactivity in the CA2/CA3a region of the adult rat hippocampus. Neurosci 93(3):955–967. https://doi.org/10.1016/s0306-4522(99)00179-7
doi: 10.1016/s0306-4522(99)00179-7
Rebola N, Pinheiro PC, Oliveira CR, Malva JO, Cunha RA (2003) Subcellular localization of adenosine A(1) receptors in nerve terminals and synapses of the rat hippocampus. Brain Res 987(1):49–58. https://doi.org/10.1016/s0006-8993(03)03247-5
doi: 10.1016/s0006-8993(03)03247-5 pubmed: 14499945
Tetzlaff W, Schubert P, Kreutzberg GW (1987) Synaptic and extrasynaptic localization of adenosine binding sites in the rat hippocampus. Neurosci 21(3):869–875. https://doi.org/10.1016/0306-4522(87)90043-1
doi: 10.1016/0306-4522(87)90043-1
Biber K, Klotz KN, Berger M, Gebicke-Härter PJ, van Calker D (1997) Adenosine A1 receptor-mediated activation of phospholipase C in cultured astrocytes depends on the level of receptor expression. J Neurosci 17(13):4956–4964. https://doi.org/10.1523/jneurosci.17-13-04956.1997
doi: 10.1523/jneurosci.17-13-04956.1997 pubmed: 9185533 pmcid: 6573309
Gebicke-Haerter PJ, Christoffel F, Timmer J, Northoff H, Berger M, Van Calker D (1996) Both adenosine A1- and A2-receptors are required to stimulate microglial proliferation. Neurochem Int 29(1):37–42
doi: 10.1016/0197-0186(95)00137-9 pubmed: 8808787
Othman T, Yan H, Rivkees SA (2003) Oligodendrocytes express functional A1 adenosine receptors that stimulate cellular migration. Glia 44(2):166–172. https://doi.org/10.1002/glia.10281
doi: 10.1002/glia.10281 pubmed: 14515332
Dixon AK, Gubitz AK, Sirinathsinghji DJ, Richardson PJ, Freeman TC (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118(6):1461–1468. https://doi.org/10.1111/j.1476-5381.1996.tb15561.x
doi: 10.1111/j.1476-5381.1996.tb15561.x pubmed: 8832073 pmcid: 1909676
Mishina M, Ishiwata K, Kimura Y, Naganawa M, Oda K, Kobayashi S, Katayama Y, Ishii K (2007) Evaluation of distribution of adenosine A2A receptors in normal human brain measured with [11C]TMSX PET. Synapse 61(9):778–784. https://doi.org/10.1002/syn.20423
doi: 10.1002/syn.20423 pubmed: 17568431
Hettinger BD, Lee A, Linden J, Rosin DL (2001) Ultrastructural localization of adenosine A2A receptors suggests multiple cellular sites for modulation of GABAergic neurons in rat striatum. J Comp Neurol 431(3):331–346. https://doi.org/10.1002/1096-9861(20010312)431:3%3c331::aid-cne1074%3e3.0.co;2-w
doi: 10.1002/1096-9861(20010312)431:3<331::aid-cne1074>3.0.co;2-w pubmed: 11170009
Rodrigues RJ, Alfaro TM, Rebola N, Oliveira CR, Cunha RA (2005) Co-localization and functional interaction between adenosine A(2A) and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum. J Neurochem 92(3):433–441. https://doi.org/10.1111/j.1471-4159.2004.02887.x
doi: 10.1111/j.1471-4159.2004.02887.x pubmed: 15659214
Rebola N, Canas PM, Oliveira CR, Cunha RA (2005) Different synaptic and subsynaptic localization of adenosine A2A receptors in the hippocampus and striatum of the rat. Neuroscience 132(4):893–903. https://doi.org/10.1016/j.neuroscience.2005.01.014
doi: 10.1016/j.neuroscience.2005.01.014 pubmed: 15857695
Li XX, Nomura T, Aihara H, Nishizaki T (2001) Adenosine enhances glial glutamate efflux via A2a adenosine receptors. Life Sci 68(12):1343–1350. https://doi.org/10.1016/s0024-3205(00)01036-5
doi: 10.1016/s0024-3205(00)01036-5 pubmed: 11388687
Nishizaki T, Nagai K, Nomura T, Tada H, Kanno T, Tozaki H, Li XX, Kondoh T, Kodama N, Takahashi E, Sakai N, Tanaka K, Saito N (2002) A new neuromodulatory pathway with a glial contribution mediated via A(2a) adenosine receptors. Glia 39(2):133–147. https://doi.org/10.1002/glia.10100
doi: 10.1002/glia.10100 pubmed: 12112365
Fiebich BL, Biber K, Lieb K, van Calker D, Berger M, Bauer J, Gebicke-Haerter PJ (1996) Cyclooxygenase-2 expression in rat microglia is induced by adenosine A2a-receptors. Glia 18(2):152–160. https://doi.org/10.1002/(sici)1098-1136(199610)18:2%3c152::aid-glia7%3e3.0.co;2-2
doi: 10.1002/(sici)1098-1136(199610)18:2<152::aid-glia7>3.0.co;2-2 pubmed: 8913778
Oldham WM, Hamm HE (2008) Heterotrimeric G protein activation by G-protein-coupled receptors. Nat Rev Mol Cell Biol 9(1):60–71. https://doi.org/10.1038/nrm2299
doi: 10.1038/nrm2299 pubmed: 18043707
Fredholm BB, IJ AP, Jacobson KA, Klotz KN, Linden J (2001) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53(4):527–552
pubmed: 11734617
Corvol JC, Studler JM, Schonn JS, Girault JA, Hervé D (2001) Galpha(olf) is necessary for coupling D1 and A2a receptors to adenylyl cyclase in the striatum. J Neurochem 76(5):1585–1588. https://doi.org/10.1046/j.1471-4159.2001.00201.x
doi: 10.1046/j.1471-4159.2001.00201.x pubmed: 11238742
Kull B, Svenningsson P, Fredholm BB (2000) Adenosine A(2A) receptors are colocalized with and activate g(olf) in rat striatum. Mol Pharmacol 58(4):771–777. https://doi.org/10.1124/mol.58.4.771
doi: 10.1124/mol.58.4.771 pubmed: 10999947
Hurley JH (1999) Structure, mechanism, and regulation of mammalian adenylyl cyclase. J Biol Chem 274(12):7599–7602. https://doi.org/10.1074/jbc.274.12.7599
doi: 10.1074/jbc.274.12.7599 pubmed: 10075642
Kopperud R, Krakstad C, Selheim F, Døskeland SO (2003) cAMP effector mechanisms. Novel twists for an ‘old’ signaling system. FEBS Lett 546(1):121–126. https://doi.org/10.1016/s0014-5793(03)00563-5
doi: 10.1016/s0014-5793(03)00563-5 pubmed: 12829247
Wainger BJ, DeGennaro M, Santoro B, Siegelbaum SA, Tibbs GR (2001) Molecular mechanism of cAMP modulation of HCN pacemaker channels. Nature 411(6839):805–810. https://doi.org/10.1038/35081088
doi: 10.1038/35081088 pubmed: 11459060
Cargnello M, Roux PP (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 75(1):50–83. https://doi.org/10.1128/MMBR.00031-10
doi: 10.1128/MMBR.00031-10 pubmed: 21372320 pmcid: 3063353
Manning BD, Cantley LC (2007) AKT/PKB signaling: navigating downstream. Cell 129(7):1261–1274. https://doi.org/10.1016/j.cell.2007.06.009
doi: 10.1016/j.cell.2007.06.009 pubmed: 17604717 pmcid: 2756685
Schulte G, Fredholm BB (2003) Signalling from adenosine receptors to mitogen-activated protein kinases. Cell Signal 15(9):813–827. https://doi.org/10.1016/s0898-6568(03)00058-5
doi: 10.1016/s0898-6568(03)00058-5 pubmed: 12834807
Schulte G, Fredholm BB (2000) Human adenosine A(1), A(2A), A(2B), and A(3) receptors expressed in Chinese hamster ovary cells all mediate the phosphorylation of extracellular-regulated kinase 1/2. Mol Pharmacol 58(3):477–482
doi: 10.1124/mol.58.3.477 pubmed: 10953039
Migita H, Kominami K, Higashida M, Maruyama R, Tuchida N, McDonald F, Shimada F, Sakurada K (2008) Activation of adenosine A1 receptor-induced neural stem cell proliferation via MEK/ERK and Akt signaling pathways. J Neurosci Res 86(13):2820–2828. https://doi.org/10.1002/jnr.21742
doi: 10.1002/jnr.21742 pubmed: 18618669
Brust TB, Cayabyab FS, Zhou N, MacVicar BA (2006) p38 mitogen-activated protein kinase contributes to adenosine A1 receptor-mediated synaptic depression in area CA1 of the rat hippocampus. J Neurosci 26(48):12427–12438. https://doi.org/10.1523/JNEUROSCI.4052-06.2006
doi: 10.1523/JNEUROSCI.4052-06.2006 pubmed: 17135404 pmcid: 6674914
Brust TB, Cayabyab FS, MacVicar BA (2007) C-Jun N-terminal kinase regulates adenosine A1 receptor-mediated synaptic depression in the rat hippocampus. Neuropharmacol 53(8):906–917. https://doi.org/10.1016/j.neuropharm.2007.09.001
doi: 10.1016/j.neuropharm.2007.09.001
Xie KQ, Zhang LM, Cao Y, Zhu J, Feng LY (2009) Adenosine A(1) receptor-mediated transactivation of the EGF receptor produces a neuroprotective effect on cortical neurons in vitro. Acta Pharmacol Sin 30(7):889–898. https://doi.org/10.1038/aps.2009.80
doi: 10.1038/aps.2009.80 pubmed: 19574994 pmcid: 4006641
Gervitz LM, Nalbant D, Williams SC, Fowler JC (2002) Adenosine-mediated activation of Akt/protein kinase B in the rat hippocampus in vitro and in vivo. Neurosci Lett 328(2):175–179. https://doi.org/10.1016/s0304-3940(02)00495-0
doi: 10.1016/s0304-3940(02)00495-0 pubmed: 12133582
Baltos JA, Gregory KJ, White PJ, Sexton PM, Christopoulos A, May LT (2016) Quantification of adenosine A(1) receptor biased agonism: implications for drug discovery. Biochem Pharmacol 99:101–112. https://doi.org/10.1016/j.bcp.2015.11.013
doi: 10.1016/j.bcp.2015.11.013 pubmed: 26581123
Dickenson JM, Hill SJ (1998) Involvement of G-protein betagamma subunits in coupling the adenosine A1 receptor to phospholipase C in transfected CHO cells. Eur J Pharmacol 355(1):85–93. https://doi.org/10.1016/s0014-2999(98)00468-3
doi: 10.1016/s0014-2999(98)00468-3 pubmed: 9754942
Freund S, Ungerer M, Lohse MJ (1994) A1 adenosine receptors expressed in CHO-cells couple to adenylyl cyclase and to phospholipase C. Naunyn Schmiedebergs Arch Pharmacol 350(1):49–56. https://doi.org/10.1007/BF00180010
doi: 10.1007/BF00180010 pubmed: 7935854
Akbar M, Okajima F, Tomura H, Shimegi S, Kondo Y (1994) A single species of A1 adenosine receptor expressed in Chinese hamster ovary cells not only inhibits cAMP accumulation but also stimulates phospholipase C and arachidonate release. Mol Pharmacol 45(5):1036–1042
pubmed: 8190094
Che J, Chan ES, Cronstein BN (2007) Adenosine A2A receptor occupancy stimulates collagen expression by hepatic stellate cells via pathways involving protein kinase A, Src, and extracellular signal-regulated kinases 1/2 signaling cascade or p38 mitogen-activated protein kinase signaling pathway. Mol Pharmacol 72(6):1626–1636. https://doi.org/10.1124/mol.107.038760
doi: 10.1124/mol.107.038760 pubmed: 17872970
Chen YC, Huang SH, Wang SM (2008) Adenosine-stimulated adrenal steroidogenesis involves the adenosine A2A and A2B receptors and the Janus kinase 2-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase signaling pathway. Int J Biochem Cell Biol 40(12):2815–2825. https://doi.org/10.1016/j.biocel.2008.05.016
doi: 10.1016/j.biocel.2008.05.016 pubmed: 18582595
Seidel MG, Klinger M, Freissmuth M, Holler C (1999) Activation of mitogen-activated protein kinase by the A(2A)-adenosine receptor via a rap1-dependent and via a p21(ras)-dependent pathway. J Biol Chem 274(36):25833–25841. https://doi.org/10.1074/jbc.274.36.25833
doi: 10.1074/jbc.274.36.25833 pubmed: 10464324
Sexl V, Mancusi G, Holler C, Gloria-Maercker E, Schutz W, Freissmuth M (1997) Stimulation of the mitogen-activated protein kinase via the A2A-adenosine receptor in primary human endothelial cells. J Biol Chem 272(9):5792–5799. https://doi.org/10.1074/jbc.272.9.5792
doi: 10.1074/jbc.272.9.5792 pubmed: 9038193
Ahmad A, Schaack JB, White CW, Ahmad S (2013) Adenosine A2A receptor-dependent proliferation of pulmonary endothelial cells is mediated through calcium mobilization, PI3-kinase and ERK1/2 pathways. Biochem Biophys Res Commun 434(3):566–571. https://doi.org/10.1016/j.bbrc.2013.03.115
doi: 10.1016/j.bbrc.2013.03.115 pubmed: 23583199 pmcid: 4046330
Mori Y, Higuchi M, Masuyama N, Gotoh Y (2004) Adenosine A2A receptor facilitates calcium-dependent protein secretion through the activation of protein kinase A and phosphatidylinositol-3 kinase in PC12 cells. Cell Struct Funct 29(4):101–110. https://doi.org/10.1247/csf.29.101
doi: 10.1247/csf.29.101 pubmed: 15665505
Perez-Aso M, Fernandez P, Mediero A, Chan ES, Cronstein BN (2014) Adenosine 2A receptor promotes collagen production by human fibroblasts via pathways involving cyclic AMP and AKT but independent of Smad2/3. FASEB J 28(2):802–812. https://doi.org/10.1096/fj.13-241646
doi: 10.1096/fj.13-241646 pubmed: 24200882 pmcid: 3898645
Boucher M, Pesant S, Falcao S, de Montigny C, Schampaert E, Cardinal R, Rousseau G (2004) Post-ischemic cardioprotection by A2A adenosine receptors: dependent of phosphatidylinositol 3-kinase pathway. J Cardiovasc Pharmacol 43(3):416–422. https://doi.org/10.1097/00005344-200403000-00013
doi: 10.1097/00005344-200403000-00013 pubmed: 15076226
Giambelluca MS, Pouliot M (2017) Early tyrosine phosphorylation events following adenosine A2A receptor in human neutrophils: identification of regulated pathways. J Leukoc Biol 102(3):829–836. https://doi.org/10.1189/jlb.2VMA1216-517R
doi: 10.1189/jlb.2VMA1216-517R pubmed: 28179537 pmcid: 5557639
Hirano D, Aoki Y, Ogasawara H, Kodama H, Waga I, Sakanaka C, Shimizu T, Nakamura M (1996) Functional coupling of adenosine A2a receptor to inhibition of the mitogen-activated protein kinase cascade in Chinese hamster ovary cells. Biochem J 316(Pt 1):81–86. https://doi.org/10.1042/bj3160081
doi: 10.1042/bj3160081 pubmed: 8645236 pmcid: 1217353
Chao MV (2003) Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 4(4):299–309. https://doi.org/10.1038/nrn1078
doi: 10.1038/nrn1078 pubmed: 12671646
Wiese S, Jablonka S, Holtmann B, Orel N, Rajagopal R, Chao MV, Sendtner M (2007) Adenosine receptor A2A-R contributes to motoneuron survival by transactivating the tyrosine kinase receptor TrkB. Proc Natl Acad Sci USA 104(43):17210–17215. https://doi.org/10.1073/pnas.0705267104
doi: 10.1073/pnas.0705267104 pubmed: 17940030 pmcid: 2040418
Fontinha BM, Diogenes MJ, Ribeiro JA, Sebastiao AM (2008) Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine. Neuropharmacol 54(6):924–933. https://doi.org/10.1016/j.neuropharm.2008.01.011
doi: 10.1016/j.neuropharm.2008.01.011
Diogenes MJ, Fernandes CC, Sebastiao AM, Ribeiro JA (2004) Activation of adenosine A2A receptor facilitates brain-derived neurotrophic factor modulation of synaptic transmission in hippocampal slices. J Neurosci 24(12):2905–2913. https://doi.org/10.1523/JNEUROSCI.4454-03.2004
doi: 10.1523/JNEUROSCI.4454-03.2004 pubmed: 15044529 pmcid: 6729859
Tebano MT, Martire A, Potenza RL, Gro C, Pepponi R, Armida M, Domenici MR, Schwarzschild MA, Chen JF, Popoli P (2008) Adenosine A(2A) receptors are required for normal BDNF levels and BDNF-induced potentiation of synaptic transmission in the mouse hippocampus. J Neurochem 104(1):279–286. https://doi.org/10.1111/j.1471-4159.2007.05046.x
doi: 10.1111/j.1471-4159.2007.05046.x pubmed: 18005343
Heese K, Fiebich BL, Bauer J, Otten U (1997) Nerve growth factor (NGF) expression in rat microglia is induced by adenosine A2a-receptors. Neurosci Lett 231(2):83–86. https://doi.org/10.1016/s0304-3940(97)00545-4
doi: 10.1016/s0304-3940(97)00545-4 pubmed: 9291146
Ciccarelli R, Di Iorio P, Bruno V, Battaglia G, D’Alimonte I, D’Onofrio M, Nicoletti F, Caciagli F (1999) Activation of A(1) adenosine or mGlu3 metabotropic glutamate receptors enhances the release of nerve growth factor and S-100beta protein from cultured astrocytes. Glia 27(3):275–281
doi: 10.1002/(SICI)1098-1136(199909)27:3<275::AID-GLIA9>3.0.CO;2-0 pubmed: 10457374
Haas HL, Selbach O (2000) Functions of neuronal adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol 362(4–5):375–381. https://doi.org/10.1007/s002100000314
doi: 10.1007/s002100000314 pubmed: 11111831
Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y (2010) Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 90(1):291–366. https://doi.org/10.1152/physrev.00021.2009
doi: 10.1152/physrev.00021.2009 pubmed: 20086079
Clark BD, Kurth-Nelson ZL, Newman EA (2009) Adenosine-evoked hyperpolarization of retinal ganglion cells is mediated by G-protein-coupled inwardly rectifying K+ and small conductance Ca2+-activated K+ channel activation. J Neurosci 29(36):11237–11245. https://doi.org/10.1523/JNEUROSCI.2836-09.2009
doi: 10.1523/JNEUROSCI.2836-09.2009 pubmed: 19741130 pmcid: 3206732
Kim CS, Johnston D (2015) A1 adenosine receptor-mediated GIRK channels contribute to the resting conductance of CA1 neurons in the dorsal hippocampus. J Neurophysiol 113(7):2511–2523. https://doi.org/10.1152/jn.00951.2014
doi: 10.1152/jn.00951.2014 pubmed: 25652929 pmcid: 4416607
Umemiya M, Berger AJ (1994) Activation of adenosine A1 and A2 receptors differentially modulates calcium channels and glycinergic synaptic transmission in rat brainstem. Neuron 13(6):1439–1446. https://doi.org/10.1016/0896-6273(94)90429-4
doi: 10.1016/0896-6273(94)90429-4 pubmed: 7993635
Yawo H, Chuhma N (1993) Preferential inhibition of omega-conotoxin-sensitive presynaptic Ca2+ channels by adenosine autoreceptors. Nature 365(6443):256–258. https://doi.org/10.1038/365256a0
doi: 10.1038/365256a0 pubmed: 8396730
Wu LG, Saggau P (1994) Adenosine inhibits evoked synaptic transmission primarily by reducing presynaptic calcium influx in area CA1 of hippocampus. Neuron 12(5):1139–1148. https://doi.org/10.1016/0896-6273(94)90321-2
doi: 10.1016/0896-6273(94)90321-2 pubmed: 8185949
Mynlieff M, Beam KG (1994) Adenosine acting at an A1 receptor decreases N-type calcium current in mouse motoneurons. J Neurosci 14(6):3628–3634
doi: 10.1523/JNEUROSCI.14-06-03628.1994 pubmed: 8207477 pmcid: 6576923
Gubitz AK, Widdowson L, Kurokawa M, Kirkpatrick KA, Richardson PJ (1996) Dual signalling by the adenosine A2a receptor involves activation of both N- and P-type calcium channels by different G proteins and protein kinases in the same striatal nerve terminals. J Neurochem 67(1):374–381. https://doi.org/10.1046/j.1471-4159.1996.67010374.x
doi: 10.1046/j.1471-4159.1996.67010374.x pubmed: 8667016
Li Q, Puro DG (2001) Adenosine activates ATP-sensitive K(+) currents in pericytes of rat retinal microvessels: role of A1 and A2a receptors. Brain Res 907(1–2):93–99. https://doi.org/10.1016/s0006-8993(01)02607-5
doi: 10.1016/s0006-8993(01)02607-5 pubmed: 11430889
Heurteaux C, Lauritzen I, Widmann C, Lazdunski M (1995) Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. Proc Natl Acad Sci USA 92(10):4666–4670. https://doi.org/10.1073/pnas.92.10.4666
doi: 10.1073/pnas.92.10.4666 pubmed: 7753861 pmcid: 42005
Popoli P, Betto P, Reggio R, Ricciarello G (1995) Adenosine A2A receptor stimulation enhances striatal extracellular glutamate levels in rats. Eur J Pharmacol 287(2):215–217. https://doi.org/10.1016/0014-2999(95)00679-6
doi: 10.1016/0014-2999(95)00679-6 pubmed: 8749040
Thompson SM, Haas HL, Gähwiler BH (1992) Comparison of the actions of adenosine at pre- and postsynaptic receptors in the rat hippocampus in vitro. J Physiol 451:347–363. https://doi.org/10.1113/jphysiol.1992.sp019168
doi: 10.1113/jphysiol.1992.sp019168 pubmed: 1403815 pmcid: 1176165
Boison D, Chen JF, Fredholm BB (2010) Adenosine signaling and function in glial cells. Cell Death Differ 17(7):1071–1082. https://doi.org/10.1038/cdd.2009.131
doi: 10.1038/cdd.2009.131 pubmed: 19763139
Burnstock G (2016) An introduction to the roles of purinergic signalling in neurodegeneration, neuroprotection and neuroregeneration. Neuropharmacol 104:4–17. https://doi.org/10.1016/j.neuropharm.2015.05.031
doi: 10.1016/j.neuropharm.2015.05.031
Woods LT, Ajit D, Camden JM, Erb L, Weisman GA (2016) Purinergic receptors as potential therapeutic targets in Alzheimer’s disease. Neuropharmacol 104:169–179. https://doi.org/10.1016/j.neuropharm.2015.10.031
doi: 10.1016/j.neuropharm.2015.10.031
Alonso-Andres P, Albasanz JL, Ferrer I, Martin M (2018) Purine-related metabolites and their converting enzymes are altered in frontal, parietal and temporal cortex at early stages of Alzheimer’s disease pathology. Brain Pathol 28(6):933–946. https://doi.org/10.1111/bpa.12592
doi: 10.1111/bpa.12592 pubmed: 29363833 pmcid: 8028663
Chang CP, Wu KC, Lin CY, Chern Y (2021) Emerging roles of dysregulated adenosine homeostasis in brain disorders with a specific focus on neurodegenerative diseases. J Biomed Sci 28(1):70. https://doi.org/10.1186/s12929-021-00766-y
doi: 10.1186/s12929-021-00766-y pubmed: 34635103 pmcid: 8507231
Angulo E, Casadó V, Mallol J, Canela EI, Viñals F, Ferrer I, Lluis C, Franco R (2003) A1 adenosine receptors accumulate in neurodegenerative structures in Alzheimer disease and mediate both amyloid precursor protein processing and tau phosphorylation and translocation. Brain Pathol 13(4):440–451. https://doi.org/10.1111/j.1750-3639.2003.tb00475.x
doi: 10.1111/j.1750-3639.2003.tb00475.x pubmed: 14655750
Albasanz JL, Perez S, Barrachina M, Ferrer I, Martín M (2008) Up-regulation of adenosine receptors in the frontal cortex in Alzheimer’s disease. Brain Pathol 18(2):211–219. https://doi.org/10.1111/j.1750-3639.2007.00112.x
doi: 10.1111/j.1750-3639.2007.00112.x pubmed: 18241242 pmcid: 8095610
Ikeda M, Mackay KB, Dewar D, McCulloch J (1993) Differential alterations in adenosine A1 and kappa 1 opioid receptors in the striatum in Alzheimer’s disease. Brain Res 616(1–2):211–217. https://doi.org/10.1016/0006-8993(93)90211-5
doi: 10.1016/0006-8993(93)90211-5 pubmed: 8395303
Kalaria RN, Sromek S, Wilcox BJ, Unnerstall JR (1990) Hippocampal adenosine A1 receptors are decreased in Alzheimer’s disease. Neurosci Lett 118(2):257–260. https://doi.org/10.1016/0304-3940(90)90641-l
doi: 10.1016/0304-3940(90)90641-l pubmed: 2274280
Fukumitsu N, Ishii K, Kimura Y, Oda K, Hashimoto M, Suzuki M, Ishiwata K (2008) Adenosine A(1) receptors using 8-dicyclopropylmethyl-1-[(11)C]methyl-3-propylxanthine PET in Alzheimer’s disease. Ann Nucl Med 22(10):841–847. https://doi.org/10.1007/s12149-008-0185-5
doi: 10.1007/s12149-008-0185-5 pubmed: 19142702
Carvalho K, Faivre E, Pietrowski MJ, Marques X, Gomez-Murcia V, Deleau A, Huin V, Hansen JN, Kozlov S, Danis C, Temido-Ferreira M, Coelho JE, Meriaux C, Eddarkaoui S, Gras SL, Dumoulin M, Cellai L, Neuro CEBBB, Landrieu I, Chern Y, Hamdane M, Buee L, Boutillier AL, Levi S, Halle A, Lopes LV, Blum D (2019) Exacerbation of C1q dysregulation, synaptic loss and memory deficits in tau pathology linked to neuronal adenosine A2A receptor. Brain 142(11):3636–3654. https://doi.org/10.1093/brain/awz288
doi: 10.1093/brain/awz288 pubmed: 31599329 pmcid: 6821333
Temido-Ferreira M, Ferreira DG, Batalha VL, Marques-Morgado I, Coelho JE, Pereira P, Gomes R, Pinto A, Carvalho S, Canas PM, Cuvelier L, Buee-Scherrer V, Faivre E, Baqi Y, Muller CE, Pimentel J, Schiffmann SN, Buee L, Bader M, Outeiro TF, Blum D, Cunha RA, Marie H, Pousinha PA, Lopes LV (2020) Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors. Mol Psychiatry 25(8):1876–1900. https://doi.org/10.1038/s41380-018-0110-9
doi: 10.1038/s41380-018-0110-9 pubmed: 29950682
Merighi S, Battistello E, Casetta I, Gragnaniello D, Poloni TE, Medici V, Cirrincione A, Varani K, Vincenzi F, Borea PA, Gessi S (2021) Upregulation of cortical A2A adenosine receptors is reflected in platelets of patients with Alzheimer’s disease. J Alzheimers Dis 80(3):1105–1117. https://doi.org/10.3233/JAD-201437
doi: 10.3233/JAD-201437 pubmed: 33646165
Liu Z, Wang F, Tang M, Zhao Y, Wang X (2019) Amyloid beta and tau are involved in sleep disorder in Alzheimer’s disease by orexin A and adenosine A(1) receptor. Int J Mol Med 43(1):435–442. https://doi.org/10.3892/ijmm.2018.3935
doi: 10.3892/ijmm.2018.3935 pubmed: 30365112
Castillo CA, Ballesteros-Yanez I, Leon-Navarro DA, Albasanz JL, Martin M (2021) Early effects of the soluble amyloid beta25–35 peptide in rat cortical neurons: modulation of signal transduction mediated by adenosine and group I metabotropic glutamate receptors. Int J Mol Sci 22(12). https://doi.org/10.3390/ijms22126577
Viana da Silva S, Haberl MG, Zhang P, Bethge P, Lemos C, Goncalves N, Gorlewicz A, Malezieux M, Goncalves FQ, Grosjean N, Blanchet C, Frick A, Nagerl UV, Cunha RA, Mulle C (2016) Early synaptic deficits in the APP/PS1 mouse model of Alzheimer’s disease involve neuronal adenosine A2A receptors. Nat Commun 7:11915. https://doi.org/10.1038/ncomms11915
doi: 10.1038/ncomms11915 pubmed: 27312972 pmcid: 4915032
Espinosa J, Rocha A, Nunes F, Costa MS, Schein V, Kazlauckas V, Kalinine E, Souza DO, Cunha RA, Porciúncula LO (2013) Caffeine consumption prevents memory impairment, neuronal damage, and adenosine A2A receptors upregulation in the hippocampus of a rat model of sporadic dementia. J Alzheimer’s dis : JAD 34(2):509–518. https://doi.org/10.3233/jad-111982
doi: 10.3233/jad-111982 pubmed: 23241554
Cao C, Loewenstein DA, Lin X, Zhang C, Wang L, Duara R, Wu Y, Giannini A, Bai G, Cai J, Greig M, Schofield E, Ashok R, Small B, Potter H, Arendash GW (2012) High blood caffeine levels in MCI linked to lack of progression to dementia. J Alzheimers Dis 30(3):559–572. https://doi.org/10.3233/JAD-2012-111781
doi: 10.3233/JAD-2012-111781 pubmed: 22430531 pmcid: 5592113
Lindsay J, Laurin D, Verreault R, Hébert R, Helliwell B, Hill GB, McDowell I (2002) Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 156(5):445–453. https://doi.org/10.1093/aje/kwf074
doi: 10.1093/aje/kwf074 pubmed: 12196314
Maia L, de Mendonça A (2002) Does caffeine intake protect from Alzheimer’s disease? Eur J Neurol 9(4):377–382. https://doi.org/10.1046/j.1468-1331.2002.00421.x
doi: 10.1046/j.1468-1331.2002.00421.x pubmed: 12099922
Ritchie K, Carrière I, de Mendonça A, Portet F, Dartigues JF, Rouaud O, Barberger-Gateau P, Ancelin ML (2007) The neuroprotective effects of caffeine. Neurol 69(6):536. https://doi.org/10.1212/01.wnl.0000266670.35219.0c
doi: 10.1212/01.wnl.0000266670.35219.0c
Santos C, Lunet N, Azevedo A, de Mendonça A, Ritchie K, Barros H (2010) Caffeine intake is associated with a lower risk of cognitive decline: a cohort study from Portugal. J Alzheimers Dis 20(Suppl 1):S175-185. https://doi.org/10.3233/jad-2010-091303
doi: 10.3233/jad-2010-091303 pubmed: 20182036
Kim JW, Byun MS, Yi D, Lee JH, Jeon SY, Jung G, Lee HN, Sohn BK, Lee JY, Kim YK, Shin SA, Sohn CH, Lee DY, Group KR (2019) Coffee intake and decreased amyloid pathology in human brain. Transl Psychiatry 9(1):270. https://doi.org/10.1038/s41398-019-0604-5
doi: 10.1038/s41398-019-0604-5 pubmed: 31641100 pmcid: 6805864
Currais A, Kato K, Canuet L, Ishii R, Tanaka T, Takeda M, Soriano S (2011) Caffeine modulates tau phosphorylation and affects Akt signaling in postmitotic neurons. J Mol Neurosci 43(3):326–332. https://doi.org/10.1007/s12031-010-9444-8
doi: 10.1007/s12031-010-9444-8 pubmed: 20838929
Arendash GW, Mori T, Cao C, Mamcarz M, Runfeldt M, Dickson A, Rezai-Zadeh K, Tane J, Citron BA, Lin X, Echeverria V, Potter H (2009) Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer’s disease mice. J Alzheimer’s dis : JAD 17(3):661–680. https://doi.org/10.3233/jad-2009-1087
doi: 10.3233/jad-2009-1087 pubmed: 19581722
Laurent C, Burnouf S, Ferry B, Batalha VL, Coelho JE, Baqi Y, Malik E, Mariciniak E, Parrot S, Van der Jeugd A, Faivre E, Flaten V, Ledent C, D’Hooge R, Sergeant N, Hamdane M, Humez S, Muller CE, Lopes LV, Buee L, Blum D (2016) A2A adenosine receptor deletion is protective in a mouse model of tauopathy. Mol Psychiatry 21(1):97–107. https://doi.org/10.1038/mp.2014.151
doi: 10.1038/mp.2014.151 pubmed: 25450226
Cunha GM, Canas PM, Melo CS, Hockemeyer J, Muller CE, Oliveira CR, Cunha RA (2008) Adenosine A2A receptor blockade prevents memory dysfunction caused by beta-amyloid peptides but not by scopolamine or MK-801. Exp Neurol 210(2):776–781. https://doi.org/10.1016/j.expneurol.2007.11.013
doi: 10.1016/j.expneurol.2007.11.013 pubmed: 18191838
Canas PM, Porciúncula LO, Cunha GM, Silva CG, Machado NJ, Oliveira JM, Oliveira CR, Cunha RA (2009) Adenosine A2A receptor blockade prevents synaptotoxicity and memory dysfunction caused by beta-amyloid peptides via p38 mitogen-activated protein kinase pathway. J Neurosci 29(47):14741–14751. https://doi.org/10.1523/jneurosci.3728-09.2009
doi: 10.1523/jneurosci.3728-09.2009 pubmed: 19940169 pmcid: 6665997
Dall’Igna OP, Porciúncula LO, Souza DO, Cunha RA, Lara DR (2003) Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity. Br J Pharmacol 138(7):1207–1209. https://doi.org/10.1038/sj.bjp.0705185
doi: 10.1038/sj.bjp.0705185 pubmed: 12711619
Dennissen FJ, Anglada-Huguet M, Sydow A, Mandelkow E, Mandelkow EM (2016) Adenosine A1 receptor antagonist rolofylline alleviates axonopathy caused by human Tau DeltaK280. Proc Natl Acad Sci USA 113(41):11597–11602. https://doi.org/10.1073/pnas.1603119113
doi: 10.1073/pnas.1603119113 pubmed: 27671637 pmcid: 5068267
Cunha RA (2005) Neuroprotection by adenosine in the brain: from A(1) receptor activation to A (2A) receptor blockade. Purinergic Signal 1(2):111–134. https://doi.org/10.1007/s11302-005-0649-1
doi: 10.1007/s11302-005-0649-1 pubmed: 18404497 pmcid: 2096528
Paul S, Elsinga PH, Ishiwata K, Dierckx RA, van Waarde A (2011) Adenosine A(1) receptors in the central nervous system: their functions in health and disease, and possible elucidation by PET imaging. Curr Med Chem 18(31):4820–4835. https://doi.org/10.2174/092986711797535335
doi: 10.2174/092986711797535335 pubmed: 21919845
Matos M, Augusto E, Machado NJ, dos Santos-Rodrigues A, Cunha RA, Agostinho P (2012) Astrocytic adenosine A2A receptors control the amyloid-beta peptide-induced decrease of glutamate uptake. J Alzheimers Dis 31(3):555–567. https://doi.org/10.3233/JAD-2012-120469
doi: 10.3233/JAD-2012-120469 pubmed: 22647260
Orr AG, Hsiao EC, Wang MM, Ho K, Kim DH, Wang X, Guo W, Kang J, Yu GQ, Adame A, Devidze N, Dubal DB, Masliah E, Conklin BR, Mucke L (2015) Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory. Nat Neurosci 18(3):423–434. https://doi.org/10.1038/nn.3930
doi: 10.1038/nn.3930 pubmed: 25622143 pmcid: 4340760
Van Zeller M, Dias D, Sebastiao AM, Valente CA (2021) NLRP3 inflammasome: a starring role in amyloid-beta- and tau-driven pathological events in Alzheimer’s disease. J Alzheimers Dis 83(3):939–961. https://doi.org/10.3233/JAD-210268
doi: 10.3233/JAD-210268 pubmed: 34366341 pmcid: 8543248
Merighi S, Nigro M, Travagli A, Pasquini S, Borea PA, Varani K, Vincenzi F, Gessi S (2022) A2A adenosine receptor: a possible therapeutic target for Alzheimer’s disease by regulating NLRP3 inflammasome activity? Int J Mol Sci 23(9). https://doi.org/10.3390/ijms23095056
Ouyang X, Ghani A, Malik A, Wilder T, Colegio OR, Flavell RA, Cronstein BN, Mehal WZ (2013) Adenosine is required for sustained inflammasome activation via the A(2)A receptor and the HIF-1alpha pathway. Nat Commun 4:2909. https://doi.org/10.1038/ncomms3909
doi: 10.1038/ncomms3909 pubmed: 24352507
Zhao W, Ma L, Cai C, Gong X (2019) Caffeine inhibits NLRP3 inflammasome activation by suppressing MAPK/NF-kappaB and A2aR signaling in LPS-induced THP-1 macrophages. Int J Biol Sci 15(8):1571–1581. https://doi.org/10.7150/ijbs.34211
doi: 10.7150/ijbs.34211 pubmed: 31360100 pmcid: 6643212
Kovacs EG, Alatshan A, Budai MM, Czimmerer Z, Biro E, Benko S (2021) Caffeine has different immunomodulatory effect on the cytokine expression and NLRP3 inflammasome function in various human macrophage subpopulations. Nutr 13(7). https://doi.org/10.3390/nu13072409
Du H, Tan Y, Li CH, Zhao Y, Li P, Ning YL, Gao RB, Wang B, Peng Y, Tan SW, Huang ZZ, Chen X, Yang N, Shan FB, Xiong RP, Zhou YG (2022) High glutamate concentration reverses the inhibitory effect of microglial adenosine 2A receptor on NLRP3 inflammasome assembly and activation. Neurosci Lett 769:136431. https://doi.org/10.1016/j.neulet.2021.136431
doi: 10.1016/j.neulet.2021.136431 pubmed: 34974110
Yang L, Yu X, Zhang Y, Liu N, Xue X, Fu J (2022) Caffeine treatment started before injury reduces hypoxic-ischemic white-matter damage in neonatal rats by regulating phenotypic microglia polarization. Pediatr Res. https://doi.org/10.1038/s41390-021-01924-6
doi: 10.1038/s41390-021-01924-6 pubmed: 36030318
Wang HQ, Song KY, Feng JZ, Huang SY, Guo XM, Zhang L, Zhang G, Huo YC, Zhang RR, Ma Y, Hu QZ, Qin XY (2022) Caffeine inhibits activation of the NLRP3 inflammasome via autophagy to attenuate microglia-mediated neuroinflammation in experimental autoimmune encephalomyelitis. J Mol Neurosci 72(1):97–112. https://doi.org/10.1007/s12031-021-01894-8
doi: 10.1007/s12031-021-01894-8 pubmed: 34478049
Cunha RA (2016) How does adenosine control neuronal dysfunction and neurodegeneration? J Neurochem 139(6):1019–1055. https://doi.org/10.1111/jnc.13724
doi: 10.1111/jnc.13724 pubmed: 27365148
Orr AG, Lo I, Schumacher H, Ho K, Gill M, Guo W, Kim DH, Knox A, Saito T, Saido TC, Simms J, Toddes C, Wang X, Yu GQ, Mucke L (2018) Istradefylline reduces memory deficits in aging mice with amyloid pathology. Neurobiol Dis 110:29–36. https://doi.org/10.1016/j.nbd.2017.10.014
doi: 10.1016/j.nbd.2017.10.014 pubmed: 29100987
Navarro G, Borroto-Escuela DO, Fuxe K, Franco R (2016) Purinergic signaling in Parkinson’s disease. Relevance for treat Neuropharmacol 104:161–168. https://doi.org/10.1016/j.neuropharm.2015.07.024
doi: 10.1016/j.neuropharm.2015.07.024
Marzagalli R, Castorina A (2015) The seeming paradox of adenosine receptors as targets for the treatment of Alzheimer’s disease: agonists or antagonists? Neural Regen Res 10(2):205–207. https://doi.org/10.4103/1673-5374.152370
doi: 10.4103/1673-5374.152370 pubmed: 25883615 pmcid: 4392664
Headrick JP, Ashton KJ, Rose’meyer RB, Peart JN (2013) Cardiovascular adenosine receptors: expression, actions and interactions. Pharmacol Ther 140(1):92–111. https://doi.org/10.1016/j.pharmthera.2013.06.002
doi: 10.1016/j.pharmthera.2013.06.002 pubmed: 23764371
Teerlink JR, Iragui VJ, Mohr JP, Carson PE, Hauptman PJ, Lovett DH, Miller AB, Pina IL, Thomson S, Varosy PD, Zile MR, Cleland JG, Givertz MM, Metra M, Ponikowski P, Voors AA, Davison BA, Cotter G, Wolko D, Delucca P, Salerno CM, Mansoor GA, Dittrich H, O’Connor CM, Massie BM (2012) The safety of an adenosine A(1)-receptor antagonist, rolofylline, in patients with acute heart failure and renal impairment: findings from PROTECT. Drug Saf 35(3):233–244. https://doi.org/10.2165/11594680-000000000-00000
doi: 10.2165/11594680-000000000-00000 pubmed: 22339573
Bjorness TE, Greene RW (2009) Adenosine and sleep. Curr Neuropharmacol 7(3):238–245. https://doi.org/10.2174/157015909789152182
doi: 10.2174/157015909789152182 pubmed: 20190965 pmcid: 2769007
Chen JF, Cunha RA (2020) The belated US FDA approval of the adenosine A2A receptor antagonist istradefylline for treatment of Parkinson’s disease. Purinergic Signal 16(2):167–174. https://doi.org/10.1007/s11302-020-09694-2
doi: 10.1007/s11302-020-09694-2 pubmed: 32236790 pmcid: 7367999
May LT, Leach K, Sexton PM, Christopoulos A (2007) Allosteric modulation of G protein-coupled receptors. Annu Rev Pharmacol Toxicol 47:1–51. https://doi.org/10.1146/annurev.pharmtox.47.120505.105159
doi: 10.1146/annurev.pharmtox.47.120505.105159 pubmed: 17009927
Christopoulos A, Changeux JP, Catterall WA, Fabbro D, Burris TP, Cidlowski JA, Olsen RW, Peters JA, Neubig RR, Pin JP, Sexton PM, Kenakin TP, Ehlert FJ, Spedding M, Langmead CJ (2014) International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands. Pharmacol Rev 66(4):918–947. https://doi.org/10.1124/pr.114.008862
doi: 10.1124/pr.114.008862 pubmed: 25026896
Wootten D, Christopoulos A, Sexton PM (2013) Emerging paradigms in GPCR allostery: implications for drug discovery. Nat Rev Drug Discov 12(8):630–644. https://doi.org/10.1038/nrd4052
doi: 10.1038/nrd4052 pubmed: 23903222
Vecchio EA, Baltos JA, Nguyen ATN, Christopoulos A, White PJ, May LT (2018) New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism. Br J Pharmacol 175(21):4036–4046. https://doi.org/10.1111/bph.14337
doi: 10.1111/bph.14337 pubmed: 29679502 pmcid: 6177620
Bruns RF, Fergus JH (1990) Allosteric enhancement of adenosine A1 receptor binding and function by 2-amino-3-benzoylthiophenes. Mol Pharmacol 38(6):939–949
pubmed: 2174510
Göblyös A (1808) Ijzerman AP (2011) Allosteric modulation of adenosine receptors. Biochim Biophys Acta 5:1309–1318. https://doi.org/10.1016/j.bbamem.2010.06.013
doi: 10.1016/j.bbamem.2010.06.013
Giorgi I, Biagi G, Bianucci AM, Borghini A, Livi O, Leonardi M, Pietra D, Calderone V, Martelli A (2008) N6–1,3-diphenylurea derivatives of 2-phenyl-9-benzyladenines and 8-azaadenines: synthesis and biological evaluation as allosteric modulators of A2A adenosine receptors. Eur J Med Chem 43(8):1639–1647. https://doi.org/10.1016/j.ejmech.2007.10.021
doi: 10.1016/j.ejmech.2007.10.021 pubmed: 18045744
Chen D, Errey JC, Heitman LH, Marshall FH, Ijzerman AP, Siegal G (2012) Fragment screening of GPCRs using biophysical methods: identification of ligands of the adenosine A(2A) receptor with novel biological activity. ACS Chem Biol 7(12):2064–2073. https://doi.org/10.1021/cb300436c
doi: 10.1021/cb300436c pubmed: 23013674
Draper-Joyce CJ, Bhola R, Wang J, Bhattarai A, Nguyen ATN, Cowie-Kent I, O’Sullivan K, Chia LY, Venugopal H, Valant C, Thal DM, Wootten D, Panel N, Carlsson J, Christie MJ, White PJ, Scammells P, May LT, Sexton PM, Danev R, Miao Y, Glukhova A, Imlach WL, Christopoulos A (2021) Positive allosteric mechanisms of adenosine A1 receptor-mediated analgesia. Nat 597(7877):571–576. https://doi.org/10.1038/s41586-021-03897-2
doi: 10.1038/s41586-021-03897-2
Draper-Joyce CJ, Khoshouei M, Thal DM, Liang YL, Nguyen ATN, Furness SGB, Venugopal H, Baltos JA, Plitzko JM, Danev R, Baumeister W, May LT, Wootten D, Sexton PM, Glukhova A, Christopoulos A (2018) Structure of the adenosine-bound human adenosine A1 receptor-Gi complex. Nature 558(7711):559–563. https://doi.org/10.1038/s41586-018-0236-6
doi: 10.1038/s41586-018-0236-6 pubmed: 29925945
Garcia-Nafria J, Lee Y, Bai X, Carpenter B, Tate CG (2018) Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein. Elife 7. https://doi.org/10.7554/eLife.35946
Garcia-Nafria J, Tate CG (2019) Cryo-EM structures of GPCRs coupled to Gs, Gi and Go. Mol Cell Endocrinol 488:1–13. https://doi.org/10.1016/j.mce.2019.02.006
doi: 10.1016/j.mce.2019.02.006 pubmed: 30930094
Ferré S, Baler R, Bouvier M, Caron MG, Devi LA, Durroux T, Fuxe K, George SR, Javitch JA, Lohse MJ, Mackie K, Milligan G, Pfleger KD, Pin JP, Volkow ND, Waldhoer M, Woods AS, Franco R (2009) Building a new conceptual framework for receptor heteromers. Nat Chem Biol 5(3):131–134. https://doi.org/10.1038/nchembio0309-131
doi: 10.1038/nchembio0309-131 pubmed: 19219011 pmcid: 2681085
Ferré S, Casadó V, Devi LA, Filizola M, Jockers R, Lohse MJ, Milligan G, Pin JP, Guitart X (2014) G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives. Pharmacol Rev 66(2):413–434. https://doi.org/10.1124/pr.113.008052
doi: 10.1124/pr.113.008052 pubmed: 24515647 pmcid: 3973609
Briddon SJ, Gandía J, Amaral OB, Ferré S, Lluís C, Franco R, Hill SJ, Ciruela F (2008) Plasma membrane diffusion of G protein-coupled receptor oligomers. Biochim Biophys Acta 1783(12):2262–2268. https://doi.org/10.1016/j.bbamcr.2008.07.006
doi: 10.1016/j.bbamcr.2008.07.006 pubmed: 18691614
Canals M, Burgueño J, Marcellino D, Cabello N, Canela EI, Mallol J, Agnati L, Ferré S, Bouvier M, Fuxe K, Ciruela F, Lluis C, Franco R (2004) Homodimerization of adenosine A2A receptors: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J Neurochem 88(3):726–734. https://doi.org/10.1046/j.1471-4159.2003.02200.x
doi: 10.1046/j.1471-4159.2003.02200.x pubmed: 14720222
Gandia J, Galino J, Amaral OB, Soriano A, Lluís C, Franco R, Ciruela F (2008) Detection of higher-order G protein-coupled receptor oligomers by a combined BRET-BiFC technique. FEBS Lett 582(20):2979–2984. https://doi.org/10.1016/j.febslet.2008.07.045
doi: 10.1016/j.febslet.2008.07.045 pubmed: 18675812
Franco R, Cordomi A, Llinas Del Torrent C, Lillo A, Serrano-Marin J, Navarro G, Pardo L (2021) Structure and function of adenosine receptor heteromers. Cell Mol Life Sci 78(8):3957–3968. https://doi.org/10.1007/s00018-021-03761-6
doi: 10.1007/s00018-021-03761-6 pubmed: 33580270
Pin JP, Neubig R, Bouvier M, Devi L, Filizola M, Javitch JA, Lohse MJ, Milligan G, Palczewski K, Parmentier M, Spedding M (2007) International Union of Basic and Clinical Pharmacology. LXVII. Recommendations for the recognition and nomenclature of G protein-coupled receptor heteromultimers. Pharmacol Rev 59(1):5–13. https://doi.org/10.1124/pr.59.1.5
doi: 10.1124/pr.59.1.5 pubmed: 17329545
Kenakin T, Miller LJ (2010) Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev 62(2):265–304. https://doi.org/10.1124/pr.108.000992
doi: 10.1124/pr.108.000992 pubmed: 20392808 pmcid: 2879912
Ferre S, Quiroz C, Woods AS, Cunha R, Popoli P, Ciruela F, Lluis C, Franco R, Azdad K, Schiffmann SN (2008) An update on adenosine A2A-dopamine D2 receptor interactions: implications for the function of G protein-coupled receptors. Curr Pharm Des 14(15):1468–1474. https://doi.org/10.2174/138161208784480108
doi: 10.2174/138161208784480108 pubmed: 18537670 pmcid: 2424285
Orru M, Bakešová J, Brugarolas M, Quiroz C, Beaumont V, Goldberg SR, Lluís C, Cortés A, Franco R, Casadó V, Canela EI, Ferré S (2011) Striatal pre- and postsynaptic profile of adenosine A(2A) receptor antagonists. PLoS ONE 6(1):e16088. https://doi.org/10.1371/journal.pone.0016088
doi: 10.1371/journal.pone.0016088 pubmed: 21264319 pmcid: 3019225
Jorg M, May LT, Mak FS, Lee KC, Miller ND, Scammells PJ, Capuano B (2015) Synthesis and pharmacological evaluation of dual acting ligands targeting the adenosine A2A and dopamine D2 receptors for the potential treatment of Parkinson’s disease. J Med Chem 58(2):718–738. https://doi.org/10.1021/jm501254d
doi: 10.1021/jm501254d pubmed: 25490054
Pulido D, Casado-Anguera V, Gomez-Autet M, Llopart N, Moreno E, Casajuana-Martin N, Ferre S, Pardo L, Casado V, Royo M (2022) Heterobivalent ligand for the adenosine A2A-dopamine D2 receptor heteromer. J Med Chem 65(1):616–632. https://doi.org/10.1021/acs.jmedchem.1c01763
doi: 10.1021/acs.jmedchem.1c01763 pubmed: 34982555
Soriano A, Ventura R, Molero A, Hoen R, Casadó V, Cortés A, Fanelli F, Albericio F, Lluís C, Franco R, Royo M (2009) Adenosine A2A receptor-antagonist/dopamine D2 receptor-agonist bivalent ligands as pharmacological tools to detect A2A–D2 receptor heteromers. J Med Chem 52(18):5590–5602. https://doi.org/10.1021/jm900298c
doi: 10.1021/jm900298c pubmed: 19711895
Borroto-Escuela DO, Carlsson J, Ambrogini P, Narváez M, Wydra K, Tarakanov AO, Li X, Millón C, Ferraro L, Cuppini R, Tanganelli S, Liu F, Filip M, Diaz-Cabiale Z, Fuxe K (2017) Understanding the role of GPCR heteroreceptor complexes in modulating the brain networks in health and disease. Front Cell Neurosci 11(37). https://doi.org/10.3389/fncel.2017.00037
Ferré S, Franco R (2010) Oligomerization of G-protein-coupled receptors: a reality. Curr Op Pharmacol 10(1):1–5. https://doi.org/10.1016/j.coph.2009.11.002
doi: 10.1016/j.coph.2009.11.002
Cristovao-Ferreira S, Navarro G, Brugarolas M, Perez-Capote K, Vaz SH, Fattorini G, Conti F, Lluis C, Ribeiro JA, McCormick PJ, Casado V, Franco R, Sebastiao AM (2013) A1R–A2AR heteromers coupled to Gs and G i/0 proteins modulate GABA transport into astrocytes. Purinergic Signal 9(3):433–449. https://doi.org/10.1007/s11302-013-9364-5
doi: 10.1007/s11302-013-9364-5 pubmed: 23657626 pmcid: 3757138
Ciruela F, Casadó V, Rodrigues RJ, Luján R, Burgueño J, Canals M, Borycz J, Rebola N, Goldberg SR, Mallol J, Cortés A, Canela EI, López-Giménez JF, Milligan G, Lluis C, Cunha RA, Ferré S, Franco R (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1–A2A receptor heteromers. J Neurosci 26(7):2080–2087. https://doi.org/10.1523/jneurosci.3574-05.2006
doi: 10.1523/jneurosci.3574-05.2006 pubmed: 16481441 pmcid: 6674939
Lillo A, Raich I, Lillo J, Perez-Olives C, Navarro G, Franco R (2022) Expression of the adenosine A2A-A3 receptor heteromer in different brain regions and marked upregulation in the microglia of the transgenic APPSw,Ind Alzheimer’s disease model. Biomed 10(2). https://doi.org/10.3390/biomedicines10020214
Farr SA, Cuzzocrea S, Esposito E, Campolo M, Niehoff ML, Doyle TM, Salvemini D (2020) Adenosine A3 receptor as a novel therapeutic target to reduce secondary events and improve neurocognitive functions following traumatic brain injury. J Neuroinflammation 17(1):339. https://doi.org/10.1186/s12974-020-02009-7
doi: 10.1186/s12974-020-02009-7 pubmed: 33183330 pmcid: 7659122
Chen GJ, Harvey BK, Shen H, Chou J, Victor A, Wang Y (2006) Activation of adenosine A3 receptors reduces ischemic brain injury in rodents. J Neurosci Res 84(8):1848–1855. https://doi.org/10.1002/jnr.21071
doi: 10.1002/jnr.21071 pubmed: 17016854
Franco R, Rivas-Santisteban R, Casanovas M, Lillo A, Saura CA, Navarro G (2020) Adenosine A2A receptor antagonists affects NMDA glutamate receptor function. Potential to Address Neurodegeneration in Alzheimer's Disease. Cells 9(5). https://doi.org/10.3390/cells9051075
Krania P, Dimou E, Bantouna M, Kouvaros S, Tsiamaki E, Papatheodoropoulos C, Sarantis K, Angelatou F (2018) Adenosine A2A receptors are required for glutamate mGluR5- and dopamine D1 receptor-evoked ERK1/2 phosphorylation in rat hippocampus: involvement of NMDA receptor. J Neurochem 145(3):217–231. https://doi.org/10.1111/jnc.14268
doi: 10.1111/jnc.14268 pubmed: 29205377
McNeill SM, Baltos JA, White PJ, May LT (2021) Biased agonism at adenosine receptors. Cell Signal 82:109954. https://doi.org/10.1016/j.cellsig.2021.109954
doi: 10.1016/j.cellsig.2021.109954 pubmed: 33610717
Ciruela F, Escriche M, Burgueno J, Angulo E, Casado V, Soloviev MM, Canela EI, Mallol J, Chan WY, Lluis C, McIlhinney RA, Franco R (2001) Metabotropic glutamate 1alpha and adenosine A1 receptors assemble into functionally interacting complexes. J Biol Chem 276(21):18345–18351. https://doi.org/10.1074/jbc.M006960200
doi: 10.1074/jbc.M006960200 pubmed: 11278325
Toms NJ, Roberts PJ (1999) Group 1 mGlu receptors elevate [Ca2+]i in rat cultured cortical type 2 astrocytes: [Ca2+]i synergy with adenosine A1 receptors. Neuropharmacology 38(10):1511–1517. https://doi.org/10.1016/s0028-3908(99)00090-8
doi: 10.1016/s0028-3908(99)00090-8 pubmed: 10530813
Yoshioka K, Hosoda R, Kuroda Y, Nakata H (2002) Hetero-oligomerization of adenosine A1 receptors with P2Y1 receptors in rat brains. FEBS Lett 531(2):299–303. https://doi.org/10.1016/S0014-5793(02)03540-8
doi: 10.1016/S0014-5793(02)03540-8 pubmed: 12417330
Fredholm BB, Assender JW, Irenius E, Kodama N, Saito N (2003) Synergistic effects of adenosine A1 and P2Y receptor stimulation on calcium mobilization and PKC translocation in DDT1 MF-2 cells. Cell Mol Neurobiol 23(3):379–400. https://doi.org/10.1023/A:1023644822539
doi: 10.1023/A:1023644822539 pubmed: 12825834
Tonazzini I, Trincavelli ML, Montali M, Martini C (2008) Regulation of A1 adenosine receptor functioning induced by P2Y1 purinergic receptor activation in human astroglial cells. J Neurosci Res 86(13):2857–2866. https://doi.org/10.1002/jnr.21727
doi: 10.1002/jnr.21727 pubmed: 18500760
Tonazzini I, Trincavelli ML, Storm-Mathisen J, Martini C, Bergersen LH (2007) Co-localization and functional cross-talk between A1 and P2Y1 purine receptors in rat hippocampus. Eur J Neurosci 26(4):890–902. https://doi.org/10.1111/j.1460-9568.2007.05697.x
doi: 10.1111/j.1460-9568.2007.05697.x pubmed: 17672857 pmcid: 2121138
Lillo A, Martinez-Pinilla E, Reyes-Resina I, Navarro G, Franco R (2020) Adenosine A2A and A3 receptors are able to interact with each other. A further piece in the puzzle of adenosine receptor-mediated signaling. Int J Mol Sci 21(14). https://doi.org/10.3390/ijms21145070
Ferré S, Karcz-Kubicha M, Hope BT, Popoli P, Burgueño J, Gutiérrez MA, Casadó V, Fuxe K, Goldberg SR, Lluis C, Franco R, Ciruela F (2002) Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: implications for striatal neuronal function. Proc Natl Acad Sci USA 99(18):11940–11945. https://doi.org/10.1073/pnas.172393799
doi: 10.1073/pnas.172393799 pubmed: 12189203 pmcid: 129373
Adams CL, Cowen MS, Short JL, Lawrence AJ (2008) Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats. Int J Neuropsychopharmacol 11(2):229–241. https://doi.org/10.1017/S1461145707007845
doi: 10.1017/S1461145707007845 pubmed: 17517168
Bogenpohl JW, Ritter SL, Hall RA, Smith Y (2012) Adenosine A2A receptor in the monkey basal ganglia: ultrastructural localization and colocalization with the metabotropic glutamate receptor 5 in the striatum. J Comp Neurol 520(3):570–589. https://doi.org/10.1002/cne.22751
doi: 10.1002/cne.22751 pubmed: 21858817 pmcid: 3338154
Nishi A, Liu F, Matsuyama S, Hamada M, Higashi H, Nairn AC, Greengard P (2003) Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling. Proc Natl Acad Sci USA 100(3):1322–1327. https://doi.org/10.1073/pnas.0237126100
doi: 10.1073/pnas.0237126100 pubmed: 12538871 pmcid: 298771
Kachroo A, Orlando LR, Grandy DK, Chen JF, Young AB, Schwarzschild MA (2005) Interactions between metabotropic glutamate 5 and adenosine A2A receptors in normal and parkinsonian mice. J Neurosci 25(45):10414–10419. https://doi.org/10.1523/jneurosci.3660-05.2005
doi: 10.1523/jneurosci.3660-05.2005 pubmed: 16280580 pmcid: 6725827
Hillion J, Canals M, Torvinen M, Casado V, Scott R, Terasmaa A, Hansson A, Watson S, Olah ME, Mallol J, Canela EI, Zoli M, Agnati LF, Ibanez CF, Lluis C, Franco R, Ferre S, Fuxe K (2002) Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 277(20):18091–18097. https://doi.org/10.1074/jbc.M107731200
doi: 10.1074/jbc.M107731200 pubmed: 11872740
Trincavelli ML, Daniele S, Orlandini E, Navarro G, Casadó V, Giacomelli C, Nencetti S, Nuti E, Macchia M, Huebner H, Gmeiner P, Rossello A, Lluís C, Martini C (2012) A new D
doi: 10.1016/j.cellsig.2011.12.018 pubmed: 22230688
Canals M, Marcellino D, Fanelli F, Ciruela F, de Benedetti P, Goldberg SR, Neve K, Fuxe K, Agnati LF, Woods AS, Ferré S, Lluis C, Bouvier M, Franco R (2003) Adenosine A2A-dopamine D2 receptor-receptor heteromerization: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J Biol Chem 278(47):46741–46749. https://doi.org/10.1074/jbc.M306451200
doi: 10.1074/jbc.M306451200 pubmed: 12933819
Kamiya T, Saitoh O, Yoshioka K, Nakata H (2003) Oligomerization of adenosine A2A and dopamine D2 receptors in living cells. Biochem Biophys Res Commun 306(2):544–549. https://doi.org/10.1016/s0006-291x(03)00991-4
doi: 10.1016/s0006-291x(03)00991-4 pubmed: 12804599
Trifilieff P, Rives ML, Urizar E, Piskorowski RA, Vishwasrao HD, Castrillon J, Schmauss C, Slättman M, Gullberg M, Javitch JA (2011) Detection of antigen interactions ex vivo by proximity ligation assay: endogenous dopamine D2-adenosine A2A receptor complexes in the striatum. Biotech 51(2):111–118. https://doi.org/10.2144/000113719
doi: 10.2144/000113719
Tanganelli S, Sandager Nielsen K, Ferraro L, Antonelli T, Kehr J, Franco R, Ferré S, Agnati LF, Fuxe K, Scheel-Krüger J (2004) Striatal plasticity at the network level. Focus on adenosine A2A and D2 interactions in models of Parkinson’s Disease. Parkinsonism Relat Disord 10(5):273–280. https://doi.org/10.1016/j.parkreldis.2004.02.015
doi: 10.1016/j.parkreldis.2004.02.015 pubmed: 15196505
Carriba P, Ortiz O, Patkar K, Justinova Z, Stroik J, Themann A, Müller C, Woods AS, Hope BT, Ciruela F, Casadó V, Canela EI, Lluis C, Goldberg SR, Moratalla R, Franco R, Ferré S (2007) Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids. Neuropsychopharmacol 32(11):2249–2259. https://doi.org/10.1038/sj.npp.1301375
doi: 10.1038/sj.npp.1301375
Soria G, Castañé A, Berrendero F, Ledent C, Parmentier M, Maldonado R, Valverde O (2004) Adenosine A2A receptors are involved in physical dependence and place conditioning induced by THC. Eur J Neurosci 20(8):2203–2213. https://doi.org/10.1111/j.1460-9568.2004.03682.x
doi: 10.1111/j.1460-9568.2004.03682.x pubmed: 15450100
Moreno E, Chiarlone A, Medrano M, Puigdellívol M, Bibic L, Howell LA, Resel E, Puente N, Casarejos MJ, Perucho J, Botta J, Suelves N, Ciruela F, Ginés S, Galve-Roperh I, Casadó V, Grandes P, Lutz B, Monory K, Canela EI, Lluís C, McCormick PJ, Guzmán M (2017) Singular location and signaling profile of adenosine A2A-cannabinoid CB1 receptor heteromers in the dorsal striatum. Neuropsychopharmacol 43(5):964–977. https://doi.org/10.1038/npp.2017.12
doi: 10.1038/npp.2017.12
Lerner TN, Horne EA, Stella N, Kreitzer AC (2010) Endocannabinoid signaling mediates psychomotor activation by adenosine A2A antagonists. J Neurosci 30(6):2160–2164. https://doi.org/10.1523/jneurosci.5844-09.2010
doi: 10.1523/jneurosci.5844-09.2010 pubmed: 20147543 pmcid: 2830732
Justinová Z, Ferré S, Redhi GH, Mascia P, Stroik J, Quarta D, Yasar S, Müller CE, Franco R, Goldberg SR (2011) Reinforcing and neurochemical effects of cannabinoid CB1 receptor agonists, but not cocaine, are altered by an adenosine A2A receptor antagonist. Addict Biol 16(3):405–415. https://doi.org/10.1111/j.1369-1600.2010.00258.x
doi: 10.1111/j.1369-1600.2010.00258.x pubmed: 21054689
Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG, Pankratz VS, Donohue MC, Trojanowski JQ (2013) Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12(2):207–216. https://doi.org/10.1016/S1474-4422(12)70291-0
doi: 10.1016/S1474-4422(12)70291-0 pubmed: 23332364 pmcid: 3622225

Auteurs

Phuc N H Trinh (PNH)

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Department of Pharmacology, Monash University, Parkville, VIC, 3052, Australia.

Jo-Anne Baltos (JA)

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Department of Pharmacology, Monash University, Parkville, VIC, 3052, Australia.

Shane D Hellyer (SD)

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.

Lauren T May (LT)

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia. lauren.may@monash.edu.
Department of Pharmacology, Monash University, Parkville, VIC, 3052, Australia. lauren.may@monash.edu.

Karen J Gregory (KJ)

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia. karen.gregory@monash.edu.
Department of Pharmacology, Monash University, Parkville, VIC, 3052, Australia. karen.gregory@monash.edu.
ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Parkville, 3052, Australia. karen.gregory@monash.edu.

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