PS1/gamma-secretase acts as rogue chaperone of glutamate transporter EAAT2/GLT-1 in Alzheimer's disease.
Humans
Alzheimer Disease
/ metabolism
Excitatory Amino Acid Transporter 2
/ metabolism
Presenilin-1
/ genetics
Amyloid Precursor Protein Secretases
/ metabolism
Male
Aged
Female
Brain
/ metabolism
Aged, 80 and over
Molecular Chaperones
/ metabolism
Fluorescence Resonance Energy Transfer
Middle Aged
Mutation
HEK293 Cells
Alzheimer’s disease
Chaperone
EAAT2
GLT-1
Gamma-secretase
Glutamate transport
Hyperactivity
Presenilin 1
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
21 Oct 2024
21 Oct 2024
Historique:
received:
04
10
2024
accepted:
13
10
2024
medline:
22
10
2024
pubmed:
22
10
2024
entrez:
21
10
2024
Statut:
epublish
Résumé
The recently discovered interaction between presenilin 1 (PS1), a subunit of γ-secretase involved in amyloid-β (Aβ) peptide production, and GLT-1, the major brain glutamate transporter (EAAT2 in the human), may link two pathological aspects of Alzheimer's disease: abnormal Aβ occurrence and neuronal network hyperactivity. In the current study, we employed a FRET-based fluorescence lifetime imaging microscopy (FLIM) to characterize the PS1/GLT-1 interaction in brain tissue from sporadic AD (sAD) patients. sAD brains showed significantly less PS1/GLT-1 interaction than those with frontotemporal lobar degeneration or non-demented controls. Familial AD (fAD) PS1 mutations, inducing a "closed" PS1 conformation similar to that in sAD brain, and gamma-secretase modulators (GSMs), inducing a "relaxed" conformation, respectively reduced and increased the interaction. Furthermore, PS1 influences GLT-1 cell surface expression and homomultimer formation, acting as a chaperone but not affecting GLT-1 stability. The diminished PS1/GLT-1 interaction suggests that these functions may not work properly in AD.
Identifiants
pubmed: 39434170
doi: 10.1186/s40478-024-01876-y
pii: 10.1186/s40478-024-01876-y
doi:
Substances chimiques
Excitatory Amino Acid Transporter 2
0
Presenilin-1
0
Amyloid Precursor Protein Secretases
EC 3.4.-
SLC1A2 protein, human
0
PSEN1 protein, human
0
Molecular Chaperones
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
166Subventions
Organisme : NIA NIH HHS
ID : AG055784
Pays : United States
Organisme : NIA NIH HHS
ID : AG15379
Pays : United States
Informations de copyright
© 2024. The Author(s).
Références
Anderson CM, Swanson RA (2000) Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32:1–14
doi: 10.1002/1098-1136(200010)32:1<1::AID-GLIA10>3.0.CO;2-W
pubmed: 10975906
Arimon M, Takeda S, Post KL, Svirsky S, Hyman BT, Berezovska O (2015) Oxidative stress and lipid peroxidation are upstream of amyloid pathology. Neurobiol Dis 84:109–119. https://doi.org/10.1016/j.nbd.2015.06.013
doi: 10.1016/j.nbd.2015.06.013
pubmed: 26102023
pmcid: 4684986
Bassan M, Liu H, Madsen KL, Armsen W, Zhou J, Desilva T, Chen W, Paradise A, Brasch MA, Staudinger J et al (2008) Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1. Eur J Neurosci 27:66–82. https://doi.org/10.1111/j.1460-9568.2007.05986.x
doi: 10.1111/j.1460-9568.2007.05986.x
pubmed: 18184314
pmcid: 4341970
Berezin MY, Achilefu S (2010) Fluorescence lifetime measurements and biological imaging. Chem Rev 110:2641–2684. https://doi.org/10.1021/cr900343z
doi: 10.1021/cr900343z
pubmed: 20356094
pmcid: 2924670
Berezovska O, Lleo A, Herl LD, Frosch MP, Stern EA, Bacskai BJ, Hyman BT (2005) Familial Alzheimer’s disease presenilin 1 mutations cause alterations in the conformation of presenilin and interactions with amyloid precursor protein. J Neurosci 25:3009–3017. https://doi.org/10.1523/jneurosci.0364-05.2005
doi: 10.1523/jneurosci.0364-05.2005
pubmed: 15772361
pmcid: 6725136
Berger UV, Hediger MA (2001) Differential distribution of the glutamate transporters GLT-1 and GLAST in tanycytes of the third ventricle. J Comp Neurol 433:101–114. https://doi.org/10.1002/cne.1128
doi: 10.1002/cne.1128
pubmed: 11283952
Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA, Mazziotta JC, Small GW (2000) Patterns of brain activation in people at risk for Alzheimer’s disease. N Engl J Med 343:450–456. https://doi.org/10.1056/nejm200008173430701
doi: 10.1056/nejm200008173430701
pubmed: 10944562
pmcid: 2831477
Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, Ratovitsky T, Prada CM, Kim G, Seekins S, Yager D et al (1996) Familial Alzheimer’s disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 17:1005–1013. https://doi.org/10.1016/s0896-6273(00)80230-5
doi: 10.1016/s0896-6273(00)80230-5
pubmed: 8938131
Busche MA, Chen X, Henning HA, Reichwald J, Staufenbiel M, Sakmann B, Konnerth A (2012) Critical role of soluble amyloid-beta for early hippocampal hyperactivity in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 109:8740–8745. https://doi.org/10.1073/pnas.1206171109
doi: 10.1073/pnas.1206171109
pubmed: 22592800
pmcid: 3365221
Chaudhry FA, Lehre KP, van Lookeren CM, Ottersen OP, Danbolt NC, Storm-Mathisen J (1995) Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry. Neuron 15:711–720. https://doi.org/10.1016/0896-6273(95)90158-2
doi: 10.1016/0896-6273(95)90158-2
pubmed: 7546749
Chen W, Aoki C, Mahadomrongkul V, Gruber CE, Wang GJ, Blitzblau R, Irwin N, Rosenberg PA (2002) Expression of a variant form of the glutamate transporter GLT1 in neuronal cultures and in neurons and astrocytes in the rat brain. J Neurosci : Off J Socfor Neurosci 22:2142–2152. https://doi.org/10.1523/JNEUROSCI.22-06-02142.2002
doi: 10.1523/JNEUROSCI.22-06-02142.2002
Chin J, Scharfman HE (2013) Shared cognitive and behavioral impairments in epilepsy and Alzheimer’s disease and potential underlying mechanisms. Epilepsy Behavior : E&B 26:343–351. https://doi.org/10.1016/j.yebeh.2012.11.040
doi: 10.1016/j.yebeh.2012.11.040
Danysz W, Parsons CG (1998) Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications. Pharmacol Rev 50:597–664
pubmed: 9860805
De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ et al (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518–522. https://doi.org/10.1038/19083
doi: 10.1038/19083
pubmed: 10206645
Dickerson BC, Salat DH, Greve DN, Chua EF, Rand-Giovannetti E, Rentz DM, Bertram L, Mullin K, Tanzi RE, Blacker D et al (2005) Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65:404–411. https://doi.org/10.1212/01.wnl.0000171450.97464.49
doi: 10.1212/01.wnl.0000171450.97464.49
pubmed: 16087905
Fan S, Xian X, Li L, Yao X, Hu Y, Zhang M, Li W (2018) ceftriaxone improves cognitive function and upregulates GLT-1-related glutamate-glutamine cycle in APP/PS1 mice. J Alzheimer’s Disease : JAD 66:1731–1743. https://doi.org/10.3233/jad-180708
doi: 10.3233/jad-180708
pubmed: 30452416
Furness DN, Dehnes Y, Akhtar AQ, Rossi DJ, Hamann M, Grutle NJ, Gundersen V, Holmseth S, Lehre KP, Ullensvang K et al (2008) A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: new insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2). Neuroscience 157:80–94. https://doi.org/10.1016/j.neuroscience.2008.08.043
doi: 10.1016/j.neuroscience.2008.08.043
pubmed: 18805467
Garcia-Esparcia P, Diaz-Lucena D, Ainciburu M, Torrejon-Escribano B, Carmona M, Llorens F, Ferrer I (2018) Glutamate transporter GLT1 expression in Alzheimer disease and dementia with Lewy bodies. Frontiers in aging neuroscience 10:122. https://doi.org/10.3389/fnagi.2018.00122
doi: 10.3389/fnagi.2018.00122
pubmed: 29755340
pmcid: 5932187
Gazestani V, Kamath T, Nadaf NM, Dougalis A, Burris SJ, Rooney B, Junkkari A, Vanderburg C, Pelkonen A, Gomez-Budia M et al (2023) Early Alzheimer’s disease pathology in human cortex involves transient cell states. Cell 186(4438–4453):e4423. https://doi.org/10.1016/j.cell.2023.08.005
doi: 10.1016/j.cell.2023.08.005
Genda EN, Jackson JG, Sheldon AL, Locke SF, Greco TM, O’Donnell JC, Spruce LA, Xiao R, Guo W, Putt M et al (2011) Co-compartmentalization of the astroglial glutamate transporter, GLT-1, with glycolytic enzymes and mitochondria. J Neurosci 31:18275–18288. https://doi.org/10.1523/JNEUROSCI.3305-11.2011
doi: 10.1523/JNEUROSCI.3305-11.2011
pubmed: 22171032
pmcid: 3259858
Gendreau S, Voswinkel S, Torres-Salazar D, Lang N, Heidtmann H, Detro-Dassen S, Schmalzing G, Hidalgo P, Fahlke C (2004) A trimeric quaternary structure is conserved in bacterial and human glutamate transporters. J Biol Chem 279:39505–39512. https://doi.org/10.1074/jbc.M408038200
doi: 10.1074/jbc.M408038200
pubmed: 15265858
Guo ZH, Mattson MP (2000) Neurotrophic factors protect cortical synaptic terminals against amyloid and oxidative stress-induced impairment of glucose transport, glutamate transport and mitochondrial function. Cerebral cortex(New York, NY : 1991) 10:50–57. https://doi.org/10.1093/cercor/10.1.50
doi: 10.1093/cercor/10.1.50
Hamidi N, Nozad A, Sheikhkanloui Milan H, Salari AA, Amani M (2019) Effect of ceftriaxone on paired-pulse response and long-term potentiation of hippocampal dentate gyrus neurons in rats with Alzheimer-like disease. Life Sci 238:116969. https://doi.org/10.1016/j.lfs.2019.116969
doi: 10.1016/j.lfs.2019.116969
pubmed: 31628912
Hascup KN, Hascup ER (2015) Altered neurotransmission prior to cognitive decline in AbetaPP/PS1 mice, a model of Alzheimer’s disease. Journal of Alzheimer’s disease : JAD 44:771–776. https://doi.org/10.3233/jad-142160
doi: 10.3233/jad-142160
pubmed: 25374106
Haugeto O, Ullensvang K, Levy LM, Chaudhry FA, Honore T, Nielsen M, Lehre KP, Danbolt NC (1996) Brain glutamate transporter proteins form homomultimers. J Biol Chem 271:27715–27722. https://doi.org/10.1074/jbc.271.44.27715
doi: 10.1074/jbc.271.44.27715
pubmed: 8910364
Hou X, Zhang X, Zou H, Guan M, Fu C, Wang W, Zhang ZR, Geng Y, Chen Y (2023) Differential and substrate-specific inhibition of gamma-secretase by the C-terminal region of ApoE2, ApoE3, and ApoE4. Neuron 111(1898–1913):e1895. https://doi.org/10.1016/j.neuron.2023.03.024
doi: 10.1016/j.neuron.2023.03.024
Huang S, Tong H, Lei M, Zhou M, Guo W, Li G, Tang X, Li Z, Mo M, Zhang X et al (2018) Astrocytic glutamatergic transporters are involved in Abeta-induced synaptic dysfunction. Brain Res 1678:129–137. https://doi.org/10.1016/j.brainres.2017.10.011
doi: 10.1016/j.brainres.2017.10.011
pubmed: 29066369
Jacob CP, Koutsilieri E, Bartl J, Neuen-Jacob E, Arzberger T, Zander N, Ravid R, Roggendorf W, Riederer P, Grunblatt E (2007) Alterations in expression of glutamatergic transporters and receptors in sporadic Alzheimer’s disease. J Alzheimer’s Disease : JAD 11:97–116. https://doi.org/10.3233/jad-2007-11113
doi: 10.3233/jad-2007-11113
pubmed: 17361039
Joutsa J, Rinne JO, Karrasch M, Hermann B, Johansson J, Anttinen A, Eskola O, Helin S, Shinnar S, Sillanpaa M (2017) Brain glucose metabolism and its relation to amyloid load in middle-aged adults with childhood-onset epilepsy. Epilepsy Res 137:69–72. https://doi.org/10.1016/j.eplepsyres.2017.09.006
doi: 10.1016/j.eplepsyres.2017.09.006
pubmed: 28950220
Kato T, Kusakizako T, Jin C, Zhou X, Ohgaki R, Quan L, Xu M, Okuda S, Kobayashi K, Yamashita K et al (2022) Structural insights into inhibitory mechanism of human excitatory amino acid transporter EAAT2. Nat Commun 13:4714. https://doi.org/10.1038/s41467-022-32442-6
doi: 10.1038/s41467-022-32442-6
pubmed: 35953475
pmcid: 9372063
Keller JN, Pang Z, Geddes JW, Begley JG, Germeyer A, Waeg G, Mattson MP (1997) Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: role of the lipid peroxidation product 4-hydroxynonenal. J Neurochem 69:273–284. https://doi.org/10.1046/j.1471-4159.1997.69010273.x
doi: 10.1046/j.1471-4159.1997.69010273.x
pubmed: 9202320
Kobayashi E, Nakano M, Kubota K, Himuro N, Mizoguchi S, Chikenji T, Otani M, Mizue Y, Nagaishi K, Fujimiya M (2018) Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain. Sci Rep 8:1712. https://doi.org/10.1038/s41598-018-19442-7
doi: 10.1038/s41598-018-19442-7
pubmed: 29374250
pmcid: 5786045
Kulijewicz-Nawrot M, Sykova E, Chvatal A, Verkhratsky A, Rodriguez JJ (2013) Astrocytes and glutamate homoeostasis in Alzheimer’s disease: a decrease in glutamine synthetase, but not in glutamate transporter-1, in the prefrontal cortex. ASN Neuro 5:273–282. https://doi.org/10.1042/an20130017
doi: 10.1042/an20130017
pubmed: 24059854
Lakowicz JR (1999) Principles of fluorescence spectroscopy. Kluwer Academic/Plenum, City
Lakowicz JR, Szmacinski H, Nowaczyk K, Berndt KW, Johnson M (1992) Fluorescence lifetime imaging. Anal Biochem 202:316–330. https://doi.org/10.1016/0003-2697(92)90112-k
doi: 10.1016/0003-2697(92)90112-k
pubmed: 1519759
pmcid: 6986422
Lakowicz JR, Szmacinski H, Nowaczyk K, Lederer WJ, Kirby MS, Johnson ML (1994) Fluorescence lifetime imaging of intracellular calcium in COS cells using Quin-2. Cell Calcium 15:7–27. https://doi.org/10.1016/0143-4160(94)90100-7
doi: 10.1016/0143-4160(94)90100-7
pubmed: 8149407
pmcid: 6906927
Larner AJ (2011) Presenilin-1 mutation Alzheimer’s disease: a genetic epilepsy syndrome? Epilepsy Behavior : E&B 21:20–22. https://doi.org/10.1016/j.yebeh.2011.03.022
doi: 10.1016/j.yebeh.2011.03.022
Lauderback CM, Hackett JM, Huang FF, Keller JN, Szweda LI, Markesbery WR, Butterfield DA (2001) The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer’s disease brain: the role of Abeta1-42. J Neurochem 78:413–416. https://doi.org/10.1046/j.1471-4159.2001.00451.x
doi: 10.1046/j.1471-4159.2001.00451.x
pubmed: 11461977
Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J, Danbolt NC (1995) Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. J Neurosci Off J Soc Neurosci 15:1835–1853. https://doi.org/10.1523/JNEUROSCI.15-03-01835.1995
doi: 10.1523/JNEUROSCI.15-03-01835.1995
Li S, Mallory M, Alford M, Tanaka S, Masliah E (1997) Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression. J Neuropathol Exp Neurol 56:901–911. https://doi.org/10.1097/00005072-199708000-00008
doi: 10.1097/00005072-199708000-00008
pubmed: 9258260
Lleo A, Berezovska O, Herl L, Raju S, Deng A, Bacskai BJ, Frosch MP, Irizarry M, Hyman BT (2004) Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation. Nat Med 10:1065–1066. https://doi.org/10.1038/nm1112
doi: 10.1038/nm1112
pubmed: 15448688
Masliah E, Alford M, DeTeresa R, Mallory M, Hansen L (1996) Deficient glutamate transport is associated with neurodegeneration in Alzheimer’s disease. Ann Neurol 40:759–766. https://doi.org/10.1002/ana.410400512
doi: 10.1002/ana.410400512
pubmed: 8957017
Matos M, Augusto E, Oliveira CR, Agostinho P (2008) Amyloid-beta peptide decreases glutamate uptake in cultured astrocytes: involvement of oxidative stress and mitogen-activated protein kinase cascades. Neuroscience 156:898–910. https://doi.org/10.1016/j.neuroscience.2008.08.022
doi: 10.1016/j.neuroscience.2008.08.022
pubmed: 18790019
McNair LF, Andersen JV, Aldana BI, Hohnholt MC, Nissen JD, Sun Y, Fischer KD, Sonnewald U, Nyberg N, Webster SC et al (2019) Deletion of neuronal GLT-1 in mice reveals its role in synaptic glutamate homeostasis and mitochondrial function. J Neurosci 39:4847–4863. https://doi.org/10.1523/jneurosci.0894-18.2019
doi: 10.1523/jneurosci.0894-18.2019
pubmed: 30926746
pmcid: 6670249
McNair LF, Andersen JV, Nissen JD, Sun Y, Fischer KD, Hodgson NW, Du M, Aoki CJ, Waagepetersen HS, Rosenberg PA et al (2020) Conditional knockout of GLT-1 in neurons leads to alterations in aspartate homeostasis and synaptic mitochondrial metabolism in striatum and hippocampus. Neurochem Res 45:1420–1437. https://doi.org/10.1007/s11064-020-03000-7
doi: 10.1007/s11064-020-03000-7
pubmed: 32144526
Mi DJ, Dixit S, Warner TA, Kennard JA, Scharf DA, Kessler ES, Moore LM, Consoli DC, Bown CW, Eugene AJ et al (2018) Altered glutamate clearance in ascorbate deficient mice increases seizure susceptibility and contributes to cognitive impairment in APP/PSEN1 mice. Neurobiol Aging 71:241–254. https://doi.org/10.1016/j.neurobiolaging.2018.08.002
doi: 10.1016/j.neurobiolaging.2018.08.002
pubmed: 30172223
pmcid: 6162152
Mookherjee P, Green PS, Watson GS, Marques MA, Tanaka K, Meeker KD, Meabon JS, Li N, Zhu P, Olson VG et al (2011) GLT-1 loss accelerates cognitive deficit onset in an Alzheimer’s disease animal model. J of Alzheimer’s Disease : JAD 26:447–455. https://doi.org/10.3233/jad-2011-110503
doi: 10.3233/jad-2011-110503
pubmed: 21677376
Pajarillo E, Rizor A, Lee J, Aschner M, Lee E (2019) The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: potential targets for neurotherapeutics. Neuropharmacol 161:107559. https://doi.org/10.1016/j.neuropharm.2019.03.002
doi: 10.1016/j.neuropharm.2019.03.002
Palop JJ, Mucke L (2009) Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol 66:435–440. https://doi.org/10.1001/archneurol.2009.15
doi: 10.1001/archneurol.2009.15
pubmed: 19204149
pmcid: 2812914
Palop JJ, Mucke L (2016) Network abnormalities and interneuron dysfunction in Alzheimer disease. Nat Rev Neurosci 17:777–792. https://doi.org/10.1038/nrn.2016.141
doi: 10.1038/nrn.2016.141
pubmed: 27829687
pmcid: 8162106
Perrin F, Sinha P, Mitchell SPC, Sadek M, Maesako M, Berezovska O (2024) Identification of PS1/gamma-secretase and glutamate transporter GLT-1 interaction sites. J Biol Chem 300:107172. https://doi.org/10.1016/j.jbc.2024.107172
doi: 10.1016/j.jbc.2024.107172
pubmed: 38499151
pmcid: 11015137
Peterson AR, Binder DK (2019) Post-translational regulation of GLT-1 in neurological diseases and its potential as an effective therapeutic target. Front Mol Neurosci 12:164. https://doi.org/10.3389/fnmol.2019.00164
doi: 10.3389/fnmol.2019.00164
pubmed: 31338020
pmcid: 6629900
Petr GT, Sun Y, Frederick NM, Zhou Y, Dhamne SC, Hameed MQ, Miranda C, Bedoya EA, Fischer KD, Armsen W et al (2015) Conditional deletion of the glutamate transporter GLT-1 reveals that astrocytic GLT-1 protects against fatal epilepsy while neuronal GLT-1 contributes significantly to glutamate uptake into synaptosomes. J Neurosci 35:5187–5201. https://doi.org/10.1523/jneurosci.4255-14.2015
doi: 10.1523/jneurosci.4255-14.2015
pubmed: 25834045
pmcid: 4380995
Pow DV, Cook DG (2009) Neuronal expression of splice variants of “glial” glutamate transporters in brains afflicted by Alzheimer’s disease: unmasking an intrinsic neuronal property. Neurochem Res 34:1748–1757. https://doi.org/10.1007/s11064-009-9957-0
doi: 10.1007/s11064-009-9957-0
pubmed: 19319679
Prikhodko O, Rynearson KD, Sekhon T, Mante MM, Nguyen PD, Rissman RA, Tanzi RE, Wagner SL (2020) The GSM BPN-15606 as a potential candidate for preventative therapy in Alzheimer’s disease. J Alzheimer’s Disease : JAD 73:1541–1554. https://doi.org/10.3233/JAD-190442
doi: 10.3233/JAD-190442
pubmed: 31958080
Proper EA, Hoogland G, Kappen SM, Jansen GH, Rensen MG, Schrama LH, van Veelen CW, van Rijen PC, van Nieuwenhuizen O, Gispen WH et al (2002) Distribution of glutamate transporters in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy. Brain 125:32–43. https://doi.org/10.1093/brain/awf001
doi: 10.1093/brain/awf001
pubmed: 11834591
Quiroz YT, Budson AE, Celone K, Ruiz A, Newmark R, Castrillon G, Lopera F, Stern CE (2010) Hippocampal hyperactivation in presymptomatic familial Alzheimer’s disease. Ann Neurol 68:865–875. https://doi.org/10.1002/ana.22105
doi: 10.1002/ana.22105
pubmed: 21194156
pmcid: 3175143
Raven F, Ward JF, Zoltowska KM, Wan Y, Bylykbashi E, Miller SJ, Shen X, Choi SH, Rynearson KD, Berezovska O et al (2017) Soluble gamma-secretase modulators attenuate Alzheimer’s beta-amyloid pathology and Induce conformational changes in presenilin 1. EBioMedicine 24:93–101. https://doi.org/10.1016/j.ebiom.2017.08.028
doi: 10.1016/j.ebiom.2017.08.028
pubmed: 28919280
pmcid: 5652037
Rimmele TS, Rosenberg PA (2016) GLT-1: The elusive presynaptic glutamate transporter. Neurochem Int 98:19–28. https://doi.org/10.1016/j.neuint.2016.04.010
doi: 10.1016/j.neuint.2016.04.010
pubmed: 27129805
pmcid: 5070539
Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke JP et al (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686. https://doi.org/10.1016/s0896-6273(00)80086-0
doi: 10.1016/s0896-6273(00)80086-0
pubmed: 8785064
Scimemi A, Meabon JS, Woltjer RL, Sullivan JM, Diamond JS, Cook DG (2013) Amyloid-beta1-42 slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1. J Neurosc : Off J Soc Neurosci 33:5312–5318. https://doi.org/10.1523/jneurosci.5274-12.2013
doi: 10.1523/jneurosci.5274-12.2013
Sogaard R, Borre L, Braunstein TH, Madsen KL, MacAulay N (2013) Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1. J Biol Chem 288:20195–20207. https://doi.org/10.1074/jbc.M113.471128
doi: 10.1074/jbc.M113.471128
pubmed: 23697999
pmcid: 3711287
Sperling RA, Laviolette PS, O’Keefe K, O’Brien J, Rentz DM, Pihlajamaki M, Marshall G, Hyman BT, Selkoe DJ, Hedden T et al (2009) Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron 63:178–188. https://doi.org/10.1016/j.neuron.2009.07.003
doi: 10.1016/j.neuron.2009.07.003
pubmed: 19640477
pmcid: 2738994
Tanaka K, Watase K, Manabe T, Yamada K, Watanabe M, Takahashi K, Iwama H, Nishikawa T, Ichihara N, Kikuchi T et al (1997) Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science (New York, NY) 276:1699–1702. https://doi.org/10.1126/science.276.5319.1699
doi: 10.1126/science.276.5319.1699
Thal DR (2002) Excitatory amino acid transporter EAAT-2 in tangle-bearing Neurons in Alzheimer’s disease. Brain Pathol 12:405–411. https://doi.org/10.1111/j.1750-3639.2002.tb00457.x
doi: 10.1111/j.1750-3639.2002.tb00457.x
Trotti D, Rizzini BL, Rossi D, Haugeto O, Racagni G, Danbolt NC, Volterra A (1997) Neuronal and glial glutamate transporters possess an SH-based redox regulatory mechanism. Eur J Neurosci 9:1236–1243. https://doi.org/10.1111/j.1460-9568.1997.tb01478.x
doi: 10.1111/j.1460-9568.1997.tb01478.x
pubmed: 9215707
Uemura K, Lill CM, Li X, Peters JA, Ivanov A, Fan Z, DeStrooper B, Bacskai BJ, Hyman BT, Berezovska O (2009) Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio. PLoS ONE 4:e7893. https://doi.org/10.1371/journal.pone.0007893
doi: 10.1371/journal.pone.0007893
pubmed: 19924286
pmcid: 2773935
Viejo L, Noori A, Merrill E, Das S, Hyman BT, Serrano-Pozo A (2022) Systematic review of human post-mortem immunohistochemical studies and bioinformatics analyses unveil the complexity of astrocyte reaction in Alzheimer’s disease. Neuropathol Appl Neurobiol 48:e12753. https://doi.org/10.1111/nan.12753
doi: 10.1111/nan.12753
pubmed: 34297416
Voglein J, Noachtar S, McDade E, Quaid KA, Salloway S, Ghetti B, Noble J, Berman S, Chhatwal J, Mori H et al (2019) Seizures as an early symptom of autosomal dominant Alzheimer’s disease. Neurobiol Aging 76:18–23. https://doi.org/10.1016/j.neurobiolaging.2018.11.022
doi: 10.1016/j.neurobiolaging.2018.11.022
pubmed: 30616208
Voglein J, Willem M, Trambauer J, Schonecker S, Dieterich M, Biskup S, Giudici C, Utz K, Oberstein T, Brendel M et al (2019) Identification of a rare presenilin 1 single amino acid deletion mutation (F175del) with unusual amyloid-beta processing effects. Neurobiol Aging 84(241):e245–e241. https://doi.org/10.1016/j.neurobiolaging.2019.08.034
doi: 10.1016/j.neurobiolaging.2019.08.034
Wagner SL, Zhang C, Cheng S, Nguyen P, Zhang X, Rynearson KD, Wang R, Li Y, Sisodia SS, Mobley WC et al (2014) Soluble gamma-secretase modulators selectively inhibit the production of the 42-amino acid amyloid beta peptide variant and augment the production of multiple carboxy-truncated amyloid beta species. Biochemistry 53:702–713. https://doi.org/10.1021/bi401537v
doi: 10.1021/bi401537v
pubmed: 24401146
Wahlster L, Arimon M, Nasser-Ghodsi N, Post KL, Serrano-Pozo A, Uemura K, Berezovska O (2013) Presenilin-1 adopts pathogenic conformation in normal aging and in sporadic Alzheimer’s disease. Acta Neuropathol 125:187–199. https://doi.org/10.1007/s00401-012-1065-6
doi: 10.1007/s00401-012-1065-6
pubmed: 23138650
Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398:513–517. https://doi.org/10.1038/19077
doi: 10.1038/19077
pubmed: 10206644
Woltjer RL, Duerson K, Fullmer JM, Mookherjee P, Ryan AM, Montine TJ, Kaye JA, Quinn JF, Silbert L, Erten-Lyons D et al (2010) Aberrant detergent-insoluble excitatory amino acid transporter 2 accumulates in Alzheimer disease. J Neuropathol Exp Neurol 69:667–676. https://doi.org/10.1097/NEN.0b013e3181e24adb
doi: 10.1097/NEN.0b013e3181e24adb
pubmed: 20535038
Wood OWG, Yeung JHY, Faull RLM, Kwakowsky A (2022) EAAT2 as a therapeutic research target in Alzheimer’s disease: a systematic review. Front Neurosci 16:952096. https://doi.org/10.3389/fnins.2022.952096
doi: 10.3389/fnins.2022.952096
pubmed: 36033606
pmcid: 9399514
Xu M, Dong Y, Wan S, Yan T, Cao J, Wu L, Bi K, Jia Y (2016) Schisantherin B ameliorates Abeta1-42-induced cognitive decline via restoration of GLT-1 in a mouse model of Alzheimer’s disease. Physiol Behav 167:265–273. https://doi.org/10.1016/j.physbeh.2016.09.018
doi: 10.1016/j.physbeh.2016.09.018
pubmed: 27660034
Yang Y, Kinney GA, Spain WJ, Breitner JC, Cook DG (2004) Presenilin-1 and intracellular calcium stores regulate neuronal glutamate uptake. J Neurochem 88:1361–1372. https://doi.org/10.1046/j.1471-4159.2003.02279.x
doi: 10.1046/j.1471-4159.2003.02279.x
pubmed: 15009636
Yernool D, Boudker O, Jin Y, Gouaux E (2004) Structure of a glutamate transporter homologue from pyrococcus horikoshii. Nature 431:811–818. https://doi.org/10.1038/nature03018
doi: 10.1038/nature03018
pubmed: 15483603
Zerangue N, Kavanaugh MP (1996) Flux coupling in a neuronal glutamate transporter. Nature 383:634–637
doi: 10.1038/383634a0
pubmed: 8857541
Zhang Z, Chen H, Geng Z, Yu Z, Li H, Dong Y, Zhang H, Huang Z, Jiang J, Zhao Y (2022) Structural basis of ligand binding modes of human EAAT2. Nat Commun 13:3329. https://doi.org/10.1038/s41467-022-31031-x
doi: 10.1038/s41467-022-31031-x
pubmed: 35680945
pmcid: 9184463
Zoltowska KM, Maesako M, Meier J, Berezovska O (2018) Novel interaction between Alzheimer’s disease-related protein presenilin 1 and glutamate transporter 1. Sci Rep 8:8718. https://doi.org/10.1038/s41598-018-26888-2
doi: 10.1038/s41598-018-26888-2
pubmed: 29880815
pmcid: 5992168
Zott B, Simon MM, Hong W, Unger F, Chen-Engerer HJ, Frosch MP, Sakmann B, Walsh DM, Konnerth A (2019) A vicious cycle of beta amyloid-dependent neuronal hyperactivation. Science (New York, NY) 365:559–565. https://doi.org/10.1126/science.aay0198
doi: 10.1126/science.aay0198
Zumkehr J, Rodriguez-Ortiz CJ, Cheng D, Kieu Z, Wai T, Hawkins C, Kilian J, Lim SL, Medeiros R, Kitazawa M (2015) Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer’s disease. Neurobiol Aging 36:2260–2271. https://doi.org/10.1016/j.neurobiolaging.2015.04.005
doi: 10.1016/j.neurobiolaging.2015.04.005
pubmed: 25964214