Role of JAK-STAT and PPAR-Gamma Signalling Modulators in the Prevention of Autism and Neurological Dysfunctions.
Autism
JAK-STAT
Neuroexcitation
Neuroinflammation
PPAR-gamma
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
02
11
2021
accepted:
23
03
2022
pubmed:
20
4
2022
medline:
1
6
2022
entrez:
19
4
2022
Statut:
ppublish
Résumé
The Janus-kinase (JAK) and signal transducer activator of transcription (STAT) signalling pathways regulate gene expression and control various factors involved in normal physiological functions such as cell proliferation, neuronal development, and cell survival. JAK activation phosphorylates STAT3 in astrocytes and microglia, and this phosphorylation has been linked to mitochondrial damage, apoptosis, neuroinflammation, reactive astrogliosis, and genetic mutations. As a regulator, peroxisome proliferator-activated receptor gamma (PPAR-gamma), in relation to JAK-STAT signalling, prevents this phosphorylation and aids in the treatment of the above-mentioned neurocomplications. Changes in cellular signalling may also contribute to the onset and progression of autism. Thus, PPAR-gamma agonist upregulation may be associated with JAK-STAT signal transduction downregulation. It may also be responsible for attenuating neuropathological changes by stimulating SOCS3 or involving RXR or SMRT, thereby reducing transcription of the various cytokine proteins and genes involved in neuronal damage. Along with JAK-STAT inhibitors, PPAR-gamma agonists could be used as target therapeutic interventions for autism. This research-based review explores the potential involvement and mutual regulation of JAK-STAT and PPAR-gamma signalling in controlling multiple pathological factors associated with autism.
Identifiants
pubmed: 35437700
doi: 10.1007/s12035-022-02819-1
pii: 10.1007/s12035-022-02819-1
doi:
Substances chimiques
PPAR gamma
0
STAT Transcription Factors
0
STAT3 Transcription Factor
0
Suppressor of Cytokine Signaling Proteins
0
Janus Kinases
EC 2.7.10.2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3888-3912Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Bousoik Emira, Aliabadi Montazeri, Hamidreza (2018) “Do We Know Jack” About JAK? A Closer Look at JAK/STAT Signaling Pathway. Front Oncol 8:287. https://doi.org/10.3389/fonc.2018.00287
doi: 10.3389/fonc.2018.00287
pubmed: 30109213
pmcid: 6079274
Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alzahrani MZ, Alshammari MA, Attia SM (2018) Resveratrol attenuates pro-inflammatory cytokines and activation of JAK1-STAT3 in BTBR T+ Itpr3tf/J autistic mice. Eur J Pharmacol 829:70–78
pubmed: 29654783
doi: 10.1016/j.ejphar.2018.04.008
Gomez-Nicola D, Fransen NL, Suzzi S, Perry VH (2013) Regulation of microglial proliferation during chronic neurodegeneration. J Neurosci 33(6):2481–2493. https://doi.org/10.1523/jneurosci.4440-12.2013
doi: 10.1523/jneurosci.4440-12.2013
pubmed: 23392676
pmcid: 6619184
Ahmad, Sheikh F Ansari, Mushtaq A Nadeem, Ahmed; Bakheet, Saleh A.; AL-Ayadhi, Laila Y.; Attia, Sabry M. 2018. Elevated IL-16 expression is associated with development of immune dysfunction in children with autism. Psychopharmacology https://doi.org/10.1007/s00213-018-5120-4
Ahmad Sheikh F, Nadeem Ahmed, Ansari Mushtaq A, Bakheet Saleh A, Laila Yousef Al-Ayadhi, Attia Sabr M (2017) Upregulation of IL-9 and JAK-STAT signaling pathway in children with autism. Prog Neuro-Psychopharmacol Biol Psychiatry 79:472–480. https://doi.org/10.1016/j.pnpbp.2017.08.002
doi: 10.1016/j.pnpbp.2017.08.002
Nadeem Ahmed, Ahmad Sheikh F, Attia Sabry M, AL-Ayadhi Laila Y, Al-Harbi Naif O, Bakheet Saleh A (2020) Dysregulation in IL-6 receptors is associated with upregulated IL-17A related signaling in CD4+ T cells of children with autism. Prog Neuro-Psychopharmacol Biol Psychiatry 97:109783. https://doi.org/10.1016/j.pnpbp.2019.109783
doi: 10.1016/j.pnpbp.2019.109783
Nadeem Ahmed, Ahmad Sheikh F, Attia Sabry M, AL-Ayadhi Laila Y, Bakheet Saleh A, Al-Harbi Naif O (2019) Oxidative and inflammatory mediators are upregulated in neutrophils of autistic children Role of IL-17A receptor signaling. Prog Neuro-Psychopharmacol Biol Psychiatry 90:204–211. https://doi.org/10.1016/j.pnpbp.2018.12.002
doi: 10.1016/j.pnpbp.2018.12.002
Napolitano M, Costa L, Palermo R, Giovenco A, Vacca A, Gulino A (2011) (2011) Protective effect of pioglitazone, a PPARγ ligand, in a 3 nitropropionic acid model of Huntington’s disease. Brain Res Bull 85(3–4):231–237. https://doi.org/10.1016/j.brainresbull.\
doi: 10.1016/j.brainresbull.\
pubmed: 21440606
Morgenweck J, Griggs RB, Donahue RR, Zadina JE, Taylor BK (2013) PPARγ activation blocks development and reduces established neuropathic pain in rats. Neuropharmacology 70:236–46. https://doi.org/10.1016/j.neuropharm.2013.01.020
doi: 10.1016/j.neuropharm.2013.01.020
pubmed: 23415633
pmcid: 3695821
Domi E, Caputi FF, Romualdi P, Domi A, Scuppa G, Candeletti S, Ubaldi M (2019) Activation of PPARγ attenuates the expression of physical and affective nicotine withdrawal symptoms through mechanisms involving amygdala and hippocampus neurotransmission. J Neurosci 39(49):9864–9875
pubmed: 31685649
pmcid: 6891057
doi: 10.1523/JNEUROSCI.1922-19.2019
Meng QQ, Feng ZC, Zhang XL, Hu LQ, Wang M, Zhang HF, Li SM (2019) PPAR-γ activation exerts an anti-inflammatory effect by suppressing the NLRP3 inflammasome in spinal cord-derived neurons. Mediators Inflamm 2019:6386729. https://doi.org/10.1155/2019/6386729.PMID:31015796;PMCID:PMC6444263
doi: 10.1155/2019/6386729.PMID:31015796;PMCID:PMC6444263
pubmed: 31015796
pmcid: 6444263
Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alsanea S, Al-Hosaini KA, Attia SM (2020) Inhibition of tyrosine kinase signaling by tyrphostin AG126 downregulates the IL-21/IL-21R and JAK/STAT pathway in the BTBR mouse model of autism. Neurotoxicology 77:1–11
pubmed: 31811869
doi: 10.1016/j.neuro.2019.12.003
Haim LB, Ceyzériat K, Carrillo-de Sauvage MA, Aubry F, Auregan G, Guillermier M, Escartin C (2015) The JAK/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer’s and Huntington’s diseases. J Neurosci 35(6):2817–2829
pubmed: 25673868
pmcid: 6605603
doi: 10.1523/JNEUROSCI.3516-14.2015
Qin H, Buckley JA, Li X, Liu Y, Fox TH 3rd, Meares GP, Yu H, Yan Z, Harms AS, Li Y, Standaert DG, Benveniste EN (2016) Inhibition of the JAK/STAT pathway protects against α-synuclein-induced neuroinflammation and dopaminergic neurodegeneration. J Neurosci 36(18):5144–5159. https://doi.org/10.1523/JNEUROSCI.4658-15.2016
doi: 10.1523/JNEUROSCI.4658-15.2016
pubmed: 27147665
pmcid: 6123006
Canto E, Isobe N, Didonna A, Hauser SL, Oksenberg JR (2018) Aberrant STAT phosphorylation signaling in peripheral blood mononuclear cells from multiple sclerosis patients. J Neuroinflammation 15(1):1–11
doi: 10.1186/s12974-018-1105-9
Kumar N, Sharma N, Khera R, Gupta R, Mehan S (2021) Guggulsterone ameliorates ethidium bromide-induced experimental model of multiple sclerosis via restoration of behavioral, molecular, neurochemical and morphological alterations in rat brain. Metab Brain Dis 36(5):911–925. https://doi.org/10.1007/s11011-021-00691-x
doi: 10.1007/s11011-021-00691-x
pubmed: 33635478
Mukthavaram R, Ouyang X, Saklecha R, Jiang P, Nomura N, Pingle SC, Kesari S (2015) Effect of the JAK2/STAT3 inhibitor SAR317461 on human glioblastoma tumorspheres. J Transl Med 13:1. https://doi.org/10.1186/s12967-015-0627-5
doi: 10.1186/s12967-015-0627-5
Hodges GE, Ménard C, Russo SJ (2016) Integrating interleukin-6 into depression diagnosis and treatment. Neurobiol Stress 4:15–22. https://doi.org/10.1016/j.ynstr.2016.03.003
doi: 10.1016/j.ynstr.2016.03.003
McGregor G, Irving AJ, Harvey J (2017) Canonical JAK-STAT signaling is pivotal for long-term depression at adult hippocampal temporoammonic-CA1 synapses. FASEB J 31(8):3449–3466. https://doi.org/10.1096/fj.201601293rr
doi: 10.1096/fj.201601293rr
pubmed: 28461339
Xu Z Zhang Z Ma X Ping F Zheng X 2015 [Effect of PM2.5 on oxidative stress-JAK/STAT signaling pathway of human bronchial epithelial cells]. Wei Sheng Yan Jiu.;44 3 451–5. Chinese. PMID: 26137628.
Tiwari A, Khera R, Rahi S, Mehan S, Makeen HA, Khormi YH, Rehman MU, Khan A (2021) Neuroprotective effect of α-mangostin in the ameliorating propionic acid-induced experimental model of autism in wistar rats. Brain Sci 11(3):288. https://doi.org/10.3390/brainsci11030288.PMID:33669120;PMCID:PMC7996534
doi: 10.3390/brainsci11030288.PMID:33669120;PMCID:PMC7996534
pubmed: 33669120
pmcid: 7996534
Rahi S. & Mehan S (2020). Understanding abnormal SMO-SHH signaling in autism spectrum disorder: potential drug target and therapeutic goals. Cell molecular neurobiolAdvance online publication https://doi.org/10.1007/s10571-020-01010-1
Peters-Scheffer N, Didden R, Korzilius H, Sturmey P (2011) A meta-analytic study on the effectiveness of comprehensive ABA-based early intervention programs for children with Autism Spectrum Disorders. Res Autism Spectr Disord 5(1):60–69. https://doi.org/10.1016/j.rasd.2010.03.011
doi: 10.1016/j.rasd.2010.03.011
Jones EK, Hanley M, Riby DM (2020) Distraction, distress and diversity: exploring the impact of sensory processing differences on learning and school life for pupils with autism spectrum disorders. Res Autism Spectr Disord 72:101515
doi: 10.1016/j.rasd.2020.101515
Chakrabarti S, Fombonne E (2001) Pervasive developmental disorders in preschool children. JAMA 285(24):3093–3099
pubmed: 11427137
doi: 10.1001/jama.285.24.3093
Rahi S, Mehan S (2020). Understanding abnormal SMO-SHH signaling in autism spectrum disorder: potential drug target and therapeutic goals. Cell mol neurobiol Advance online publ 10.1007/s10571-020-01010-1
Lord C, Elsabbagh M, Baird G, Veenstra-Vanderweele J (2018) Autism spectrum disorder. Lancet 392(10146):508–520
pubmed: 30078460
pmcid: 7398158
doi: 10.1016/S0140-6736(18)31129-2
Attia, SM.; Al-Hamamah, MA.; Ahmad, SF.; Nadeem, A.; Attia, MSM.; Ansari, MA.; Bakheet, SA.; Al-Ayadhi, LY. 2019. Evaluation of DNA repair efficiency in autistic children by molecular cytogenetic analysis and transcriptome profiling. DNA Repair, 102750 https://doi.org/10.1016/j.dnarep.2019.102750
Mehan S, Rahi S, Tiwari A, Kapoor T, Rajdev K, Sharma R, Khera H, Kosey S, Kukkar U, Dudi R (2020) Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats. Neural Regen Res 15(6):1140–1149. https://doi.org/10.4103/1673-5374.270316
doi: 10.4103/1673-5374.270316
pubmed: 31823895
Gadow KD, DeVincent CJ, Pomeroy J, Azizian A (2004) Psychiatric symptoms in preschool children with PDD and clinic and comparison samples. J Autism Dev Disord 34(4):379–393
pubmed: 15449514
doi: 10.1023/B:JADD.0000037415.21458.93
Lecavalier L (2006) Behavioural and emotional problems in young people with pervasive developmental disorders: relative prevalence, effects of subject characteristics, and empirical classification. J Autism Dev Disord 36(8):1101–1114. https://doi.org/10.1007/s10803-006-0147-5
doi: 10.1007/s10803-006-0147-5
pubmed: 16897387
Nadeem, Ahmed; Ahmad, Sheikh F.; Al-Harbi, Naif O.; AL-Ayadhi, Laila Y.; Attia, Sabry M.; Alasmari, Abdullah F; As Sobeai, Homood M; Bakheet, Saleh A. 2020. Ubiquitous plasticizer, Di-(2-ethylhexyl) phthalate enhances existing inflammatory profile in monocytes of children with autism. Toxicology, 152597 https://doi.org/10.1016/j.tox.2020.152597
Darnall JE, Kerr JIM, Stark GR (1994) Jak-Stat pathways and transcriptional activation in response to IFNs and other extra cellular signaling protein. Science 264:1415–1421
doi: 10.1126/science.8197455
Berger J, Moller DE (2002) The mechanisms of action of PPARs. Annu Rev Med 53(1):409–435
pubmed: 11818483
doi: 10.1146/annurev.med.53.082901.104018
Warden A, Truitt J, Merriman M, Ponomareva O, Jameson K, Ferguson LB, Mayfield RD, Harris RA (2016) Localization of PPAR isotypes in the adult mouse and human brain. Sci Rep 6:27618. https://doi.org/10.1038/srep27618
doi: 10.1038/srep27618
pubmed: 27283430
pmcid: 4901333
Schintu N, Frau L, Ibba M, Caboni P, Garau A, Carboni E, Carta AR (2009) PPAR-gamma-mediated neuroprotection in a chronic mouse model of Parkinson’s disease. Eur J Neurosci 29(5):954–963. https://doi.org/10.1111/j.1460-9568.2009.06657.x
doi: 10.1111/j.1460-9568.2009.06657.x
pubmed: 19245367
Stopponi S, de Guglielmo G, Somaini L, Cippitelli A, Cannella N, Kallupi M, Ubaldi M, Heilig M, Demopulos G, Gaitanaris G, Ciccocioppo R (2013) Activation of PPARγ by pioglitazone potentiates the effects of naltrexone on alcohol drinking and relapse in msP rats. Alcohol Clin Exp Res 37(8):1351–1360. https://doi.org/10.1111/acer.12091
doi: 10.1111/acer.12091
pubmed: 23550625
Storer PD, Xu J, Chavis J, Drew PD (2005) Peroxisome proliferator-activated receptor-gamma agonists inhibit the activation of microglia and astrocytes: implications for multiple sclerosis. J Neuroimmunol 161(1–2):113–122. https://doi.org/10.1016/j.jneuroim.2004.12.015
doi: 10.1016/j.jneuroim.2004.12.015
pubmed: 15748950
De-Fraja C, Conti L, Magrassi L, Govoni S, Cattaneo E (1998) Members of the JAK/STAT proteins are expressed and regulated during development in the mammalian forebrain. J Neurosci Res 54(3):320–330
pubmed: 9819137
doi: 10.1002/(SICI)1097-4547(19981101)54:3<320::AID-JNR3>3.0.CO;2-R
Csabai D, Seress L, Varga Z, Ábrahám H, Miseta A, Wiborg O, Czéh B (2017) 2017 Electron microscopic analysis of hippocampal axo-somatic synapses in a chronic stress model for depression. Hippocampus 27(1):17–27. https://doi.org/10.1002/hipo.22650
doi: 10.1002/hipo.22650
pubmed: 27571571
Welch JS, Ricote M, Akiyama TE, Gonzalez FJ, Glass CK (2003) PPAR gamma and PPAR delta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages. Proc Natl Acad Sci U S A 100(11):6712–7. https://doi.org/10.1073/pnas.1031789100
doi: 10.1073/pnas.1031789100
pubmed: 12740443
pmcid: 164512
Napimoga MH, Vieira SM, Dal-Secco D, Freitas A, Souto FO, Mestriner FL, Alves-Filho JC, Grespan R, Kawai T, Ferreira SH, Cunha FQ (2008) Peroxisome proliferator-activated receptor-gamma ligand, 15-deoxy-Delta 12,14-prostaglandin J2, reduces neutrophil migration via a nitric oxide pathway. J Immunol 180(1):609–617. https://doi.org/10.4049/jimmunol.180.1.609
doi: 10.4049/jimmunol.180.1.609
pubmed: 18097063
Harris SG, Phipps RP (2001) The nuclear receptor PPAR-gamma is expressed by mouse T lymphocytes and PPAR-gamma agonists induce apoptosis. Eur J Immunol 31(4):1098–1105. https://doi.org/10.1002/1521-4141(200104)31:4%3c1098::aid-immu1098%3e3.0.co;2-i
doi: 10.1002/1521-4141(200104)31:4<1098::aid-immu1098>3.0.co;2-i
pubmed: 11298334
Padilla J, Leung E, Phipps RP (2002 Apr) Human B lymphocytes and B lymphomas express PPAR-gamma and are killed by PPAR-gamma agonists. Clin Immunol 103(1):22–33. https://doi.org/10.1006/clim.2001.5181
doi: 10.1006/clim.2001.5181
pubmed: 11987982
Garza JC, Guo M, Zhang W, Lu XY (2008) 2008 Leptin increases adult hippocampal neurogenesis in vivo and in vitro. J Biol Chem 283(26):18238–47. https://doi.org/10.1074/jbc.M800053200
doi: 10.1074/jbc.M800053200
pubmed: 18367451
pmcid: 2440628
A Tiwari S Rahi S Mehan 2020 Elucidation of abnormal extracellular regulated kinase (ERK) signaling and associations with syndromic and non-syndromic autism Curr Drug Targets.Advanceonlinepublication. https://doi.org/10.2174/1389450121666201020155010
Singh RK, Jia C, Garcia F, Carrasco GA, Battaglia G, Muma NA (2010) Activation of the JAK-STAT pathway by olanzapine is necessary for desensitization of serotonin2A receptor-stimulated phospholipase C signaling in rat frontal cortex but not serotonin2A receptor-stimulated hormone release. J Psychopharmacol 24(7):1079–88. https://doi.org/10.1177/0269881109103090
doi: 10.1177/0269881109103090
pubmed: 19304867
Orellana DI, Quintanilla RA, Gonzalez-Billault C, Maccioni RB (2005) Role of the JAKs/STATs pathway in the intracellular calcium changes induced by interleukin-6 in hippocampal neurons. Neurotox Res 8(3–4):295–304. https://doi.org/10.1007/BF03033983
doi: 10.1007/BF03033983
pubmed: 16371324
Gu J, Li G, Sun T, Su Y, Zhang X, Shen J, Tian Z, Zhang J (2008) Blockage of the STAT3 signaling pathway with a decoy oligonucleotide suppresses growth of human malignant glioma cells. J Neurooncol 89(1):9–17. https://doi.org/10.1007/s11060-008-9590-9
doi: 10.1007/s11060-008-9590-9
pubmed: 18415045
Tsai MC, Chen WJ, Tsai MS, Ching CH, Chuang JI (2011) Melatonin attenuates brain contusion-induced oxidative insult, inactivation of signal transducers and activators of transcription 1, and upregulation of suppressor of cytokine signaling-3 in rats. J Pineal Res 51(2):233–245. https://doi.org/10.1111/j.1600-079X.2011.00885.x
doi: 10.1111/j.1600-079X.2011.00885.x
pubmed: 21545521
R Wafer P Tandon JEN Minchin 2017 The role of peroxisome proliferator-activated receptor gamma (PPARG) in adipogenesis: applying knowledge from the fish aquaculture industry to biomedical research Front Endocrinol (Lausanne) 8102 https://doi.org/10.3389/fendo.2017.00102
Heming M, Gran S, Jauch SL, Fischer-Riepe L, Russo A, Klotz L, Hermann S, Schäfers M, Roth J, Barczyk-Kahlert K (2018) Peroxisome proliferator-activated receptor-γ modulates the response of macrophages to lipopolysaccharide and glucocorticoids. Front Immunol 9:893. https://doi.org/10.3389/fimmu.2018.00893
doi: 10.3389/fimmu.2018.00893
pubmed: 29867927
pmcid: 5949563
Jiang C, Ting AT, Seed B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391(6662):82–86. https://doi.org/10.1038/34184
doi: 10.1038/34184
pubmed: 9422509
Abdullah Z, Geiger S, Nino-Castro A, Böttcher JP, Muraliv E, Gaidt M, Klotz L (2012) Lack of PPARγ in myeloid cells confers resistance to Listeria monocytogenes infection. PloS one 7(5):e37349
doi: 10.2310/JIM.0b013e3181659972
pubmed: 18317435
Abdullah Z, Geiger S, Nino-Castro A, Böttcher JP, Muraliv E, Gaidt M, Klotz L (2012) Lack of PPARγ in myeloid cells confers resistance to Listeria monocytogenes infection. PloS one 7(5):e37349
pubmed: 22629382
pmcid: 3357414
doi: 10.1371/journal.pone.0037349
Bouhlel MA, Derudas B, Rigamonti E, Dièvart R, Brozek J, Haulon S, Chinetti-Gbaguidi G (2007) PPARγ activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab 6(2):137–143
pubmed: 17681149
doi: 10.1016/j.cmet.2007.06.010
Eslami H, Sharifi AM, Rahimi H, Rahati M (2014) Protective effect of telmisartan against oxidative damage induced by high glucose in neuronal PC12 cell. Neurosci Lett 558:31–36
pubmed: 24211690
doi: 10.1016/j.neulet.2013.10.057
Zhao Y, Patzer A, Gohlke P, Herdegen T, Culman J (2005) The intracerebral application of the PPARγ-ligand pioglitazone confers neuroprotection against focal ischaemia in the rat brain. Eur J Neurosci 22(1):278–282. https://doi.org/10.1111/j.1460-9568.2005.04200.x
doi: 10.1111/j.1460-9568.2005.04200.x
pubmed: 16029218
Zhao X, Strong R, Zhang J, Sun G, Tsien JZ, Cui Z, Grotta JC, Aronowski J (2009) Neuronal PPAR-gamma deficiency increases susceptibility to brain damage after cerebral ischemia. J Neurosci 29(19):6186–6195. https://doi.org/10.1523/JNEUROSCI.5857-08.2009
doi: 10.1523/JNEUROSCI.5857-08.2009
pubmed: 19439596
pmcid: 2739014
Combs CK, Bates P, Karlo JC, Landreth GE (2001) Regulation of β-amyloid stimulated pro-inflammatory responses by peroxisome proliferator-activated receptor α. Neurochem Int 39(5–6):449–457
pubmed: 11578780
doi: 10.1016/S0197-0186(01)00052-3
Diab A, Hussain RZ, Lovett-Racke AE, Chavis JA, Drew PD, Racke MK (2004) Ligands for the peroxisome proliferator-activated receptor-γ and the retinoid X receptor exert additive anti-inflammatory effects on experimental autoimmune encephalomyelitis. J Neuroimmunol 148(1–2):116–126
pubmed: 14975592
doi: 10.1016/j.jneuroim.2003.11.010
Yu JH, Kim KH, Kim H (2007) SOCS 3 and PPAR-gamma ligands inhibit the expression of IL-6 and TGF-beta1 by regulating JAK2/STAT3 signaling in pancreas. Int J Biochem Cell Biol 40(4):677–88. https://doi.org/10.1016/j.biocel.2007.10.007
doi: 10.1016/j.biocel.2007.10.007
pubmed: 18035585
Song EA, Lim JW, Kim H (2017) Docosahexaenoic acid inhibits IL-6 expression via PPARγ-mediated expression of catalase in cerulein-stimulated pancreatic acinar cells. Int J Biochem Cell Biol 88:60–68. https://doi.org/10.1016/j.biocel.2017.05.011
doi: 10.1016/j.biocel.2017.05.011
pubmed: 28483666
Nicholson SE, De Souza D, Fabri LJ, Corbin J, Willson TA, Zhang J-G, Baca M (2000) Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130. Proc Natl Acad Sci 97(12):6493–6498. https://doi.org/10.1073/pnas.100135197
doi: 10.1073/pnas.100135197
pubmed: 10829066
pmcid: 18633
Ju KD, Lim JW, Kim H (2017) Peroxisome proliferator-activated receptor-gamma inhibits the activation of in cerulein-stimulated pancreatic acinar cells. J Cancer Prev 22(3):189–194. https://doi.org/10.15430/JCP.2017.22.3.189
doi: 10.15430/JCP.2017.22.3.189
pubmed: 29018784
pmcid: 5624460
Li Q, Wang M, Tan L, Wang C, Ma J, Li N, Li J (2005) Docosahexaenoic acid changes lipid composition and interleukin-2 receptor signaling in membrane rafts. J Lipid Res 46(9):1904–1913. https://doi.org/10.1194/jlr.m500033-jlr200
doi: 10.1194/jlr.m500033-jlr200
pubmed: 15930520
Natarajan C, Bright JJ (2002) Peroxisome proliferator-activated receptor-gamma agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation. Genes Immun 3(2):59–70. https://doi.org/10.1038/sj.gene.6363832
doi: 10.1038/sj.gene.6363832
pubmed: 11960303
Gulbins A, Grassmé H, Hoehn R, Kohnen M, Edwards MJ, Kornhuber J, Gulbins E (2016) Role of Janus-kinases in major depressive disorder. Neurosignals 2016 24(1):71–80. https://doi.org/10.1159/000442613
doi: 10.1159/000442613
Nicolas CS, Peineau S, Amici M, Csaba Z, Fafouri A, Javalet C, Collett VJ, Hildebrandt L, Seaton G, Choi SL, Sim SE, Bradley C, Lee K, Zhuo M, Kaang BK, Gressens P, Dournaud P, Fitzjohn SM, Bortolotto ZA, Cho K, Collingridge GL (2012) The Jak/STAT pathway is involved in synaptic plasticity. Neuron 73(2):374–390. https://doi.org/10.1016/j.neuron
doi: 10.1016/j.neuron
pubmed: 22284190
pmcid: 3268861
Wang X, Liu Q, Ihsan A, Huang L, Dai M, Hao H, Cheng G, Liu Z, Wang Y, Yuan Z (2012) JAK/STAT pathway plays a critical role in the pro-inflammatory gene expression and apoptosis of RAW264.7 cells induced by trichothecenes as DON and T-2 toxin. Toxicol Sci 127(2):412–24. https://doi.org/10.1093/toxsci/kfs106
doi: 10.1093/toxsci/kfs106
pubmed: 22454431
Chin YE, Kitagawa M, Kuida K, Flavell RA, Fu XY (1997) Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis. Mol Cell Biol 17(9):5328–5337
pubmed: 9271410
pmcid: 232383
doi: 10.1128/MCB.17.9.5328
Charras A, Arvaniti P, Le Dantec C, Dalekos GN, Zachou K, Bordron A, Renaudineau Y (2019) JAK inhibitors and oxidative stress control. Front Immunol 10:2814
pubmed: 31867003
pmcid: 6908489
doi: 10.3389/fimmu.2019.02814
Wang XL, Qiao CM, Liu JO, Li CY (2017) Inhibition of the SOCS1-JAK2-STAT3 signaling pathway confers neuroprotection in rats with ischemic stroke. Cell Physiol Biochem 44(1):85–98. https://doi.org/10.1159/000484585
doi: 10.1159/000484585
pubmed: 29130998
Chez MG, Dowling T, Patel PB, Khanna P, Kominsky M (2007) Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol 36(6):361–365
pubmed: 17560496
doi: 10.1016/j.pediatrneurol.2007.01.012
Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA (2005) Neuroglial activation and neuroinflammation in the brain of patients with autism. Erratum In Ann Neurol 57(1):67–81. https://doi.org/10.1002/ana.20315
doi: 10.1002/ana.20315
Lee N, Jae Y, Kim M, Cho T, Lee C, Hong YR, Hyeon DY, Ahn S, Kwon H, Kim K, Jung JH, Chae S, Shin JO, Bok J, Byun Y, Hwang D, Koo J (2020) A pathogen-derived metabolite induces microglial activation via odorant receptors. FEBS J 287(17):3841–3870. https://doi.org/10.1111/febs.15234
doi: 10.1111/febs.15234
pubmed: 32003140
Korbecki J, Bobiński R, Dutka M (2019) Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors. Inflamm Res. https://doi.org/10.1007/s00011-019-01231-1
doi: 10.1007/s00011-019-01231-1
pubmed: 31363792
pmcid: 6813288
Millot P, San C, Bennana E, Porte B, Vignal N, Hugon J, Mouton-Liger F (2020) STAT3 inhibition protects against neuroinflammation and BACE1 upregulation induced by systemic inflammation. Immunol Lett. https://doi.org/10.1016/j.imlet.2020.10.004
doi: 10.1016/j.imlet.2020.10.004
pubmed: 33096140
Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T, Kishimoto T (1993) IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science 260(5115):1808–1810. https://doi.org/10.1126/science.8511589
doi: 10.1126/science.8511589
pubmed: 8511589
Schmidt S, Moric E, Schmidt M, Sastre M, Feinstein DL, Heneka MT (2004) Anti-inflammatory and antiproliferative actions of PPAR-gamma agonists on T lymphocytes derived from MS patients. J Leukoc Biol 75(3):478–485. https://doi.org/10.1189/jlb.0803402
doi: 10.1189/jlb.0803402
pubmed: 14657213
Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391(6662):79–82. https://doi.org/10.1038/34178
doi: 10.1038/34178
pubmed: 9422508
Khera R, Mehan S, Bhalla S, Kumar S, Alshammari A, Alharbi M, Sadhu SS (2022) Guggulsterone mediated JAK/STAT and PPAR-gamma modulation prevents neurobehavioral and neurochemical abnormalities in propionic acid-induced experimental model of autism. Molecules 27:889
pubmed: 35164154
pmcid: 8839522
doi: 10.3390/molecules27030889
Piochon C, Kano M, Hansel C (2016) LTD-like molecular pathways in developmental synaptic pruning. Nat Neurosci 19(10):1299–1310. https://doi.org/10.1038/nn.4389
doi: 10.1038/nn.4389
pubmed: 27669991
pmcid: 5070480
Hansel C (2019) 2018 Deregulation of synaptic plasticity in autism. Neurosci Lett 1(688):58–61. https://doi.org/10.1016/j.neulet.2018.02.003
doi: 10.1016/j.neulet.2018.02.003
Huttenlocher PR (1990) Morphometric study of human cerebral cortex development. Neuropsychologia 28(6):517–527. https://doi.org/10.1016/0028-3932(90)90031-i
doi: 10.1016/0028-3932(90)90031-i
pubmed: 2203993
Farshbaf MJ, Ghaedi K, Shirani M, Nasr-Esfahani MH (2014) Peroxisome proliferator activated receptor gamma (PPARγ) as a therapeutic target for improvement of cognitive performance in Fragile-X. Med Hypotheses 82(3):291–294. https://doi.org/10.1016/j.mehy.2013.12.012
doi: 10.1016/j.mehy.2013.12.012
pubmed: 24456944
D’ Angelo M, Castelli V, Catanesi M, Antonosante A, Dominguez-Benot R, Ippoliti R, Cimini A (2019) PPARγ and cognitive performance. Int J Mol Sci 20(20):5068. https://doi.org/10.3390/ijms20205068
doi: 10.3390/ijms20205068
Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L (2009) Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem 42(10–11):1032–1040
pubmed: 19306862
doi: 10.1016/j.clinbiochem.2009.03.011
Nadeem, Ahmed; Ahmad, Sheikh F.; Al-Harbi, Naif O.; Alasmari, Abdullah F.; AL-Ayadhi, Laila Y.; Alasmari, Fawaz; Ibrahim, Khalid E.; Attia, Sabry M.; Bakheet, Saleh A. 2020. Upregulation of enzymatic antioxidants in CD4+ T cells of autistic children. Biochimie, 171–172 205–212 https://doi.org/10.1016/j.biochi.2020.03.009
Rose S, Melnyk S, Pavliv O, Bai S, Nick TG, Frye RE, James SJ (2012) Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry 2(7) e134 https://doi.org/10.1038/tp.2012.61
doi: 10.1038/tp.2012.61
pubmed: 22781167
pmcid: 3410618
Nadeem, Ahmed; Ahmad, Sheikh F.; Attia, Sabry M.; Bakheet, Saleh A.; Al-Harbi, Naif O.; AL-Ayadhi, Laila Y. 2017. Activation of IL-17 receptor leads to increased oxidative inflammation in peripheral monocytes of autistic children. Brain, Behavior, and Immunity, S0889159117304257–. https://doi.org/10.1016/j.bbi.2017.09.010
Qu Y, Oyan AM, Liu R, Hua Y, Zhang J, Hovland R, Popa M, Liu X, Brokstad KA, Simon R, Molven A, Lin B, Zhang WD, McCormack E, Kalland KH, Ke XS (2013) Generation of prostate tumor-initiating cells is associated with elevation of reactive oxygen species and IL-6/STAT3 signaling. Cancer Res 73(23):7090–7100. https://doi.org/10.1158/0008-5472.CAN-13-1560
doi: 10.1158/0008-5472.CAN-13-1560
pubmed: 24101153
Waris G, Huh KW, Siddiqui A (2001) Mitochondrially associated hepatitis B virus X protein constitutively activates transcription factors STAT-3 and NF-kappa B via oxidative stress. Mol Cell Biol 21(22):7721–7730. https://doi.org/10.1128/MCB.21.22.7721-7730.2001
doi: 10.1128/MCB.21.22.7721-7730.2001
pubmed: 11604508
pmcid: 99943
Nadeem Ahmed, Ahmad Sheikh F, Attia Sabry M, AL-Ayadhi Laila Y, Al-Harbi Naif O, Bakheet Saleh A (2019) Dysregulated enzymatic antioxidant network in peripheral neutrophils and monocytes in children with autism. Prog Neuro-Psychopharmacology Biol Psychiatry 88:352–359. https://doi.org/10.1016/j.pnpbp.2018.08.020
doi: 10.1016/j.pnpbp.2018.08.020
Manea A, Tanase LI, Raicu M, Simionescu M (2010) Jak/STAT signaling pathway regulates nox1 and nox4-based NADPH oxidase in human aortic smooth muscle cells. ArteriosclerThrombVasc Biol 30(1):105–112. https://doi.org/10.1161/ATVBAHA.109.193896
doi: 10.1161/ATVBAHA.109.193896
Al-Harbi Naif O, Ahmed Nadeem, Ahmad Sheikh F, AL-Ayadhi Laila Y, Al-Harbi Mohammad M, As Sobeai Homood M, Ibrahim Khalid E, Bakheet Saleh A (2020) Elevated expression of toll-like receptor 4 is associated with NADPH oxidase-induced oxidative stress in B cells of children with autism. Int Immunopharmacol 84:106555. https://doi.org/10.1016/j.intimp.2020.106555
doi: 10.1016/j.intimp.2020.106555
pubmed: 32388012
Ahmed Nadeem, Ahmad Sheikh F, Bakheet Saleh A, Al-Harbi Naif O, AL-Ayadhi Laila Y, Attia Sabry M, Zoheir Khairy MA (2017) Toll-like receptor 4 signaling is associated with upregulated NADPH oxidase expression in peripheral T cells of children with autism. Brain Behav Immun 61:146–154. https://doi.org/10.1016/j.bbi.2016.12.024
doi: 10.1016/j.bbi.2016.12.024
Giampietro L, Gallorini M, De Filippis B, Amoroso R, Cataldi A, di Giacomo V (2019) PPAR-γ agonist GL516 reduces oxidative stress and apoptosis occurrence in a rat astrocyte cell line. Neurochem Int 126:239–245. https://doi.org/10.1016/j.neuint.2019.03.021
doi: 10.1016/j.neuint.2019.03.021
pubmed: 30946848
Chandra M, Miriyala S, Panchatcharam M (2017) PPARγand Its Role in Cardiovascular Diseases. PPAR Res 2017:1–10. https://doi.org/10.1155/2017/6404638
doi: 10.1155/2017/6404638
Randy LH, Guoying B (2007) Agonism of peroxisome proliferator receptor-gamma may have therapeutic potential for neuroinflammation and Parkinson’s disease. Curr Neuropharmacol 5(1):35–46. https://doi.org/10.2174/157015907780077123
doi: 10.2174/157015907780077123
pubmed: 18615152
pmcid: 2435341
Gupte AA, Liu JZ, Ren Y, Minze LJ, Wiles JR, Collins AR, Lyon CJ, Pratico D, Finegold MJ, Wong ST, Webb P, Baxter JD, Moore DD, Hsueh WA (2012) Rosiglitazone attenuates age- and diet-associated nonalcoholic steatohepatitis in male low-density lipoprotein receptor knockout mice. Hepatology 526:2001–11. https://doi.org/10.1002/hep.2394
doi: 10.1002/hep.2394
Chiang MC, Chern Y, Huang RN (2012) PPARgamma rescue of the mitochondrial dysfunction in Huntington’s disease. Neurobiol Dis 45(1):322–328. https://doi.org/10.1016/j.nbd.2011.08.016
doi: 10.1016/j.nbd.2011.08.016
pubmed: 21907283
Gurney JG, McPheeters ML, Davis MM (2006) Parental report of health conditions and health care use among children with and without autism: national survey of children’s health. Arch PediatrAdolesc Med 160(8):825–830. https://doi.org/10.1001/archpedi.160.8.825
doi: 10.1001/archpedi.160.8.825
Albert, P. R., &Benkelfat, C. 2013 The neurobiology of depression—revisiting the serotonin hypothesis. II. Genetic, epigenetic and clinical studies.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiat 67(5):446–457
pubmed: 20015486
doi: 10.1016/j.biopsych.2009.09.033
Haapakoski R, Mathieu J, Ebmeier KP, Alenius H, Kivimäki M (2015) Cumulative meta-analysis of interleukins 6 and 1β tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain Behav Immun 49:206–15. https://doi.org/10.1016/j.bbi.2015.06.001
doi: 10.1016/j.bbi.2015.06.001
pubmed: 26065825
pmcid: 4566946
Kong E, Sucic S, Monje FJ, Savalli G, Diao W, Khan D, Ronovsky M, Cabatic M, Koban F, Freissmuth M, Pollak DD (2015) STAT3 controls IL6-dependent regulation of serotonin transporter function and depression-like behaviour. Erratum In Sci Rep 5:9009. https://doi.org/10.1038/srep09009
doi: 10.1038/srep09009
Guan X, Wang Q, Liu M, Sun A, Li X. 2020 Possible involvement of the IL-6/JAK2/STAT3 pathway in the hypothalamus in depressive-like behaviour of rats exposed to chronic mild stress. Neuropsychobiology.:1–9. https://doi.org/10.1159/000509908 . Epub ahead of print.
Al-Samhari MM, Al-Rasheed NM, Al-Rejaie S, Al-Rasheed NM, Hasan IH, Mahmoud AM, Dzimiri N (2016) Possible involvement of the JAK/STAT signaling pathway in N-acetylcysteine-mediated antidepressant-like effects. Exp Biol Med 241(5):509–518
doi: 10.1177/1535370215619707
Beheshti, F., Hosseini, M., Hashemzehi, M., Soukhtanloo, M., &Asghari, A. 2019 The effects of PPAR-γ agonist pioglitazone on anxiety and depression-like behaviours in lipopolysaccharide injected rats. Toxin Rev, 1–10.
Kemp DE, Schinagle M, Gao K, Conroy C, Ganocy SJ, Ismail-Beigi F, Calabrese JR (2014) PPAR-γ agonism as a modulator of mood: proof-of-concept for pioglitazone in bipolar depression. CNS Drugs 28(6):571–581. https://doi.org/10.1007/s40263-014-0158-2
doi: 10.1007/s40263-014-0158-2
pubmed: 24715548
pmcid: 4113193
Chauhan A, Gu F, Essa MM, Wegiel J, Kaur K, Brown WT, Chauhan V (2011) Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism. J Neurochem 117(2):209–220
pubmed: 21250997
pmcid: 4839269
doi: 10.1111/j.1471-4159.2011.07189.x
Graf WD, Marin-Garcia J, Gao HG, Pizzo S, Naviaux RK, Markusic D, Barshop BA, Courchesne E, Haas RH (2000) Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation. J Child Neurol 15(6):357–361. https://doi.org/10.1177/088307380001500601
doi: 10.1177/088307380001500601
pubmed: 10868777
Abid H, Ryan ZC, Delmotte P, Sieck GC, Lanza IR (2020) Extramyocellular interleukin-6 influences skeletal muscle mitochondrial physiology through canonical JAK/STAT signaling pathways. FASEB J 34(11):14458–14472
pubmed: 32885495
doi: 10.1096/fj.202000965RR
Wilson-Fritch L, Nicoloro S, Chouinard M, Lazar MA, Chui PC, Leszyk J, Straubhaar J, Czech MP, Corvera S (2004) Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest 114(9):1281–1289. https://doi.org/10.1172/JCI21752
doi: 10.1172/JCI21752
pubmed: 15520860
pmcid: 524228
Rong JX, Klein JL, Qiu Y, Xie M, Johnson JH, Waters KM, Zhang V, Kashatus JA, Remlinger KS, Bing N, Crosby RM, Jackson TK, Witherspoon SM, Moore JT, Ryan TE, Neill SD, Strum JC (2011) Rosiglitazone induces mitochondrial biogenesis in differentiated murine 3T3-L1 and C3H/10T1/2 adipocytes. PPAR Res 2011:179454. https://doi.org/10.1155/2011/179454
doi: 10.1155/2011/179454
pubmed: 22013433
pmcid: 3195302
El-Ansary, A., Zayed, N., Al-Ayadhi, L., Qasem, H., Anwar, M., Meguid, N. A.,&Bjørklund, G. 2019. GABA synaptopathy promotes the elevation of caspases 3 and 9 as pro-apoptotic markers in Egyptian patients with autism spectrum disorder. Acta NeurologicaBelgica, 1–13.
Eftekharian MM, Komaki A, Oskooie VK, Namvar A, Taheri M, Ghafouri-Fard S (2019) Assessment of apoptosis pathway in peripheral blood of autistic patients. J Mol Neurosci 69(4):588–596
pubmed: 31363911
doi: 10.1007/s12031-019-01387-9
Rozovski U, Harris DM, Li P, Liu Z, Wu JY, Grgurevic S, Faderl S, Ferrajoli A, Wierda WG, Martinez M, Verstovsek S, Keating MJ, Estrov Z (2016) At high levels, constitutively activated stat3 induces apoptosis of chronic lymphocytic leukemia cells. J Immunol 196(10):4400–9. https://doi.org/10.4049/jimmunol.1402108
doi: 10.4049/jimmunol.1402108
pubmed: 27076684
Fuenzalida K, Quintanilla R, Ramos P, Piderit D, Fuentealba RA, Martinez G, Bronfman M (2007) Peroxisome proliferator-activated receptor γ up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis. J Biol Chem 282(51):37006–37015
pubmed: 17965419
doi: 10.1074/jbc.M700447200
Lin H, Lin TN, Cheung WM, Nian GM, Tseng PH, Chen SF, Chen JJ, Shyue SK, Liou JY, Wu CW, Wu (2002) KK Cyclooxygenase-1 and bicistronic cyclooxygenase-1/prostacyclin synthase gene transfer protect against ischemic cerebral infarction. Circulation 105(16):1962–9. https://doi.org/10.1161/01.cir.0000015365.49180.05
doi: 10.1161/01.cir.0000015365.49180.05
pubmed: 11997284
Yang C, Jo SH, Csernus B, Hyjek E, Liu Y, Chadburn A, Wang YL (2007) Activation of peroxisome proliferator-activated receptor gamma contributes to the survival of T lymphoma cells by affecting cellular metabolism. Am J Pathol 170(2):722–732. https://doi.org/10.2353/ajpath.2007.060651
doi: 10.2353/ajpath.2007.060651
pubmed: 17255338
pmcid: 1851856
Anderson LT, Campbell M, Grega DM, Perry R, Small AM, Green WH (1984) Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms. Am J Psychiatry 141(10):1195–1202. https://doi.org/10.1176/ajp.141.10.1195
doi: 10.1176/ajp.141.10.1195
pubmed: 6385731
Anderson LT, Campbell M, Adams P, Small AM, Perry R, Shell J (1989) The effects of haloperidol on discrimination learning and behavioural symptoms in autistic children. J Autism Dev Disord 19(2):227–239
pubmed: 2663834
doi: 10.1007/BF02211843
Comings DE, Comings BG, Muhleman D, Dietz G, Shahbahrami B, Tast D, Flanagan SD (1991) The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA 266(13):1793–1800
pubmed: 1832466
doi: 10.1001/jama.1991.03470130073032
Nakamura K, Sekine Y, Ouchi Y, Tsujii M, Yoshikawa E, Futatsubashi M, Tsuchiya KJ, Sugihara G, Iwata Y, Suzuki K, Matsuzaki H, Suda S, Sugiyama T, Takei N, Mori N (2010) Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. Arch Gen Psychiatry 67(1):59–68. https://doi.org/10.1001/archgenpsychiatry.2009.137
doi: 10.1001/archgenpsychiatry.2009.137
pubmed: 20048223
Chao OY, Pathak SS, Zhang H, Dunaway N, Li JS, Mattern C, Yang YM (2020) Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism. Mol Brain 13(1):1–16
doi: 10.1186/s13041-020-00649-7
Berhow MT, Hiroi N, Kobierski LA, Hyman SE, Nestler EJ (1996) Influence of cocaine on the JAK–STAT pathway in the mesolimbic dopamine system. J Neurosci 16(24):8019–8026
pubmed: 8987828
pmcid: 6579209
doi: 10.1523/JNEUROSCI.16-24-08019.1996
Dehmer T, Heneka MT, Sastre M, Dichgans J, Schulz JB (2004) Protection by pioglitazone in the MPTP model of Parkinson’s disease correlates with IκBα induction and block of NFκB and iNOS activation. J Neurochem 88(2):494–501
pubmed: 14690537
doi: 10.1046/j.1471-4159.2003.02210.x
Collin M, Thiemermann C (2003) The PPAR-γ ligand 15-deoxyΔ12, 14 prostaglandin J2 reduces the liver injury in endotoxic shock. Eur J Pharmacol 476(3):257–258
pubmed: 12969773
doi: 10.1016/S0014-2999(03)02179-4
Collin M, Patel NS, Dugo L, Thiemermann C (2004) Role of peroxisome proliferator-activated receptor-γ in the protection afforded by 15-deoxyΔ12, 14 prostaglandin J2 against the multiple organ failure caused by endotoxin. Crit Care Med 32(3):826–831
pubmed: 15090969
doi: 10.1097/01.CCM.0000114821.25573.E7
Kim EJ, Kwon KJ, Park JY, Lee SH, Moon CH, Baik EJ (2002) Effects of peroxisome proliferator-activated receptor agonists on LPS-induced neuronal death in mixed cortical neurons: associated with iNOS and COX-2. Brain Res 941(1–2):1–10. https://doi.org/10.1016/s0006-8993(02)02480-0
doi: 10.1016/s0006-8993(02)02480-0
pubmed: 12031542
Jamain S, Quach H, Betancur C, Råstam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T (2003) Paris Autism Research International Sibpair Study Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34(1):27–29. https://doi.org/10.1038/ng1136
doi: 10.1038/ng1136
pubmed: 12669065
pmcid: 1925054
Yan J, Oliveira G, Coutinho A, Yang C, Feng J, Katz C, Sram J, Bockholt A, Jones IR, Craddock N, Cook EH Jr, Vicente A, Sommer SS (2005) Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol Psychiatry 10(4):329–332. https://doi.org/10.1038/sj.mp.4001629
doi: 10.1038/sj.mp.4001629
pubmed: 15622415
Etherton M, Földy C, Sharma M, Tabuchi K, Liu X, Shamloo M, Südhof TC (2011) Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. Proc Natl Acad Sci 108(33):13764–13769
pubmed: 21808020
pmcid: 3158170
doi: 10.1073/pnas.1111093108
D’Gama AM, Pochareddy S, Li M, Jamuar SS, Reiff RE, Lam ATN, Walsh CA (2015) Targeted DNA sequencing from autism spectrum disorder brains implicates multiple genetic mechanisms. Neuron 88(5):910–917
pubmed: 26637798
pmcid: 4672379
doi: 10.1016/j.neuron.2015.11.009
Nord AS, Roeb W, Dickel DE, Walsh T, Kusenda M, O’Connor KL, Malhotra D, McCarthy SE, Stray SM, Taylor SM, Sebat J (2011 Jun) STAART Psychopharmacology Network King B King MC McClellan JM 2011 Reduced transcript expression of genes affected by inherited and de novo CNVs in autism. Eur J Hum Genet 19(6):727–31. https://doi.org/10.1038/ejhg.2011.24
doi: 10.1038/ejhg.2011.24
pubmed: 21448237
pmcid: 3110052
Halgren C, Kjaergaard S, Bak M, Hansen C, El-Schich Z, Anderson CM, Henriksen KF, Hjalgrim H, Kirchhoff M, Bijlsma EK, Nielsen M, den Hollander NS, Ruivenkamp CA, Isidor B, Le Caignec C, Zannolli R, Mucciolo M, Renieri A, Mari F, Anderlid BM, Andrieux J, Dieux A, Tommerup N, Bache I (2012 Sep) 2011 Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Clin Genet 82(3):248–55. https://doi.org/10.1111/j.1399-0004.2011.01755.x
doi: 10.1111/j.1399-0004.2011.01755.x
pubmed: 21801163
pmcid: 3464360
Santen GW, Aten E, Sun Y, Almomani R, Gilissen C, Nielsen M, Kant SG, Snoeck IN, Peeters EA, Hilhorst-Hofstee Y, Wessels MW, den Hollander NS, Ruivenkamp CA, van Ommen GJ, Breuning MH, den Dunnen JT, van Haeringen A, Kriek M (2012) Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome. Nat Genet 44(4):379–380. https://doi.org/10.1038/ng.2217
doi: 10.1038/ng.2217
pubmed: 22426309
Shibutani M, Horii T, Shoji H, Morita S, Kimura M, Terawaki N, Miyakawa T, Hatada I (2017) Arid1b haploinsufficiency causes abnormal brain gene expression and autism-related behaviours in mice. Int J Mol Sci 18(9):1872. https://doi.org/10.3390/ijms18091872
doi: 10.3390/ijms18091872
pmcid: 5618521
O’Callaghan JP, Kelly KA, VanGilder RL, Sofroniew MV, Miller DB (2014) Early activation of STAT3 regulates reactive astrogliosis induced by diverse forms of neurotoxicity. PLoS ONE 9(7):e102003. https://doi.org/10.1371/journal.pone.0102003
doi: 10.1371/journal.pone.0102003
pubmed: 25025494
pmcid: 4098997
Chen E, Xu D, Lan X, Jia B, Sun L, C Zheng J, Peng H (2013) A novel role of the STAT3 pathway in brain inflammation-induced human neural progenitor cell differentiation. Curr Mol Med 13(9):1474–1484
pubmed: 23971732
pmcid: 4157724
doi: 10.2174/15665240113139990076
Chen S, Dong Z, Cheng M, Zhao Y, Wang M, Sai N, Zhang X (2017) Homocysteine exaggerates microglia activation and neuroinflammation through microglia localized STAT3 overactivation following ischemic stroke. J Neuroinflammation 14(1):1–12
doi: 10.1186/s12974-016-0779-0
Chen XM, Yu YH, Wang L, Zhao XY, Li JR (2019) Effect of the JAK2/STAT3 signaling pathway on nerve cell apoptosis in rats with white matter injury. Eur Rev Med Pharmacol Sci 23(1):321–327
pubmed: 30657573
Duan W, Yang Y, Yi W, Yan J, Liang Z, Wang N, Yi D (2013) New Role of JAK2/STAT3 Signaling in endothelial cell oxidative stress injury and protective effect of melatonin. PLoS ONE 8(3):e57941. https://doi.org/10.1371/journal.pone.0057941
doi: 10.1371/journal.pone.0057941
pubmed: 23483946
pmcid: 3590213
Wang B, Wang X, Yang S, Liu X, Feng D, Lu F, Gao G (2016) Neuroprotective effects of nitidine in Parkinson’s disease models through inhibiting microglia activation: role of the Jak2–Stat3 pathway. RSC Adv 6(75):71328–71337. https://doi.org/10.1039/c6ra11759g
doi: 10.1039/c6ra11759g
Reichenbach N, Delekate A, Plescher M, Schmitt F, Krauss S, Blank N, Halle A, Petzold GC (2019) Inhibition of Stat3-mediated astrogliosis ameliorates pathology in an Alzheimer’s disease model. EMBO Mol Med 11(2):e9665. https://doi.org/10.15252/emmm.201809665
doi: 10.15252/emmm.201809665
pubmed: 30617153
pmcid: 6365929
Shibata N, Yamamoto T, Hiroi A, Omi Y, Kato Y, Kobayashi M (2009) Activation of STAT3 and inhibitory effects of pioglitazone on STAT3 activity in a mouse model of SOD1 mutated amyotrophic lateral sclerosis. Neuropathology 2010 Aug 30(4):353–360. https://doi.org/10.1111/j.1440-1789.2009.01078.x
doi: 10.1111/j.1440-1789.2009.01078.x
Zhu YF, Wang WP, Zheng XF, Chen Z, Chen T, Huang ZY, Jia LJ, Lei WL (2020) Characteristic response of striatal astrocytes to dopamine depletion. Neural Regen Res 15(4):724–730. https://doi.org/10.4103/1673-5374.266917
doi: 10.4103/1673-5374.266917
pubmed: 31638097
Hao Y, Yang X, Chen C, Yuan-Wang, Wang X, Li M, Yu Z. (2010) STAT3 signalling pathway is involved in the activation of microglia induced by 2.45 GHz electromagnetic fields. Int J Radiat Biol.;86(1):27–36. https://doi.org/10.3109/09553000903264507 . PMID: 20070213.
Sarmiento Soto, M., Larkin, J. R., Martin, C., Khrapitchev, A. A., Maczka, M., Economopoulos, V. Sibson, N. R. 2020. STAT3-mediated astrocyte reactivity associated with brain metastasis contributes to neurovascular dysfunction. Cancer Research, canres.2251.2020. https://doi.org/10.1158/0008-5472.can-20-2251
Chen, S. L., Cai, G. X., Ding, H. G., Liu, X. Q., Wang, Z. H., Jing, Y. W., ... & Wen, M. Y 2020 JAK/STAT signaling pathway-mediated microRNA-181b promoted blood-brain barrier impairment by targeting sphingosine-1-phosphate receptor 1 in septic rats. Annals Transl Med 8 21
Tan MSY, Sandanaraj E, Chong YK, Lim SW, Koh LWH, Ng WH, Tan NS, Tan P, Ang BT, Tang C (2019) A STAT3-based gene signature stratifies glioma patients for targeted therapy. Nat Commun 10(1):3601. https://doi.org/10.1038/s41467-019-11614-x
doi: 10.1038/s41467-019-11614-x
pubmed: 31399589
pmcid: 6689009
West AJ, Tsui V, Stylli SS, Nguyen HPT, Morokoff AP, Kaye AH, Luwor RB (2018) The role of interleukin-6-STAT3 signalling in glioblastoma. Oncol Lett 16:44095–4104. https://doi.org/10.3892/ol.2018.9227
doi: 10.3892/ol.2018.9227
McFarland BC, Ma JY, Langford CP, Gillespie GY, Yu H, Zheng Y, Nozell SE, Huszar D, Benveniste EN (2011) Therapeutic potential of AZD1480 for the treatment of human glioblastoma. Mol Cancer Ther 10(12):2384–93. https://doi.org/10.1158/1535-7163.MCT-11-0480
doi: 10.1158/1535-7163.MCT-11-0480
pubmed: 22027691
pmcid: 3237864
Träger U, Magnusson A, Lahiri Swales N, Wild E, North J, Lowdell M, Björkqvist M. 2013 ho JAK/STAT signalling in Huntington’s disease immune cells. PLoSCurr.Dec 13;5 https://doi.org/10.1371/currents.hd.5791c897b5c3bebeed93b1d1da0c0648
Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schäffer AA, Puck JM, Grimbacher B (2007) STAT3 mutations in the hyper-IgE syndrome. N Engl J Med 357(16):1608–1619. https://doi.org/10.1056/NEJMoa073687
doi: 10.1056/NEJMoa073687
pubmed: 17881745
Liu S, Liu X, Xiong H, Wang W, Liu Y, Yin L, Tu C, Wang H, Xiang X, Xu J, Duan B, Tao A, Zhao Z, Mei Z (2019) CXCL13/CXCR5 signaling contributes to diabetes-induced tactile allodynia via activating pERK, pSTAT3, pAKT pathways and pro-inflammatory cytokines production in the spinal cord of male mice. Brain Behav Immun 80:711–724. https://doi.org/10.1016/j.bbi.2019.05.020
doi: 10.1016/j.bbi.2019.05.020
pubmed: 31100371
Wang LH, Yang XY, Zhang X, Huang J, Hou J, Li J, Farrar WL (2004) Transcriptional inactivation of STAT3 by PPARγ suppresses IL-6-responsive multiple myeloma cells. Immunity 20(2):205–218
pubmed: 14975242
doi: 10.1016/S1074-7613(04)00030-5
Guo T, Wang Y, Guo Y, Wu S, Chen W, Liu N, Wang Y, Geng D (2018) (2018) 1, 25–D3 Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-γ Activation. Front Cell Neurosci 17(12):480. https://doi.org/10.3389/fncel.2018.00480
doi: 10.3389/fncel.2018.00480
Keledjian K, Tsymbalyuk O, Semick S, Moyer M, Negoita S, Kim K, Ivanova S, Gerzanich V, Simard JM (2020) The peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone, ameliorates neurofunctional and neuroinflammatory abnormalities in a rat model of Gulf War Illness. PLoS ONE 15(11):e0242427. https://doi.org/10.1371/journal.pone.0242427
doi: 10.1371/journal.pone.0242427
pubmed: 33186383
pmcid: 7665704
Carta AR, Frau L, Pisanu A, Wardas J, Spiga S, Carboni E (2011) Rosiglitazone decreases peroxisome proliferator receptor-γ levels in microglia and inhibits TNF-α production: new evidences on neuroprotection in a progressive Parkinson’s disease model. Neuroscience 194:250–261. https://doi.org/10.1016/j.neuroscience.2011.07.046
doi: 10.1016/j.neuroscience.2011.07.046
pubmed: 21839812
Abd El-Abhar H, El Fattah MA, Wadie W, El-Tanbouly DM (2018) Cilostazol disrupts TLR-4 Akt/GSK-3β/CREB and IL-6/JAK-2/STAT-3/SOCS-3 crosstalk in a rat model of Huntington’s disease. Plos one 13(9):e0203837
doi: 10.1371/journal.pone.0203837
Jensen KV, Cseh O, Aman A, Weiss S, Luchman HA (2017) The JAK2/STAT3 inhibitor pacritinib effectively inhibits patient-derived GBM brain tumor initiating cells in vitro and when used in combination with temozolomide increases survival in an orthotopic xenograft model. PLoS ONE 12(12):e0189670. https://doi.org/10.1371/journal.pone.0189670
doi: 10.1371/journal.pone.0189670
pubmed: 29253028
pmcid: 5734728
Damm J, Harden LM, Gerstberger R, Roth J, Rummel C (2013) The putative JAK-STAT inhibitor AG490 exacerbates LPS-fever, reduces sickness behaviour, and alters the expression of pro-and anti-inflammatory genes in the rat brain. Neuropharmacology 71:98–111
pubmed: 23548702
doi: 10.1016/j.neuropharm.2013.03.014
Al DU, Ji TL, Yang B, Cao JF, Zhang XG, Li Y, Pan S, Zhang B, Hu ZB, Zeng XW (2013) Neuroprotective effect of AG490 in experimental traumatic brain injury of rats. Chin Med J (Engl) 126(15):2934–2937
Choi M, Kim H, Yang EJ, Kim HS (2020) Inhibition of STAT3 phosphorylation attenuates impairments in learning and memory in 5XFAD mice, an animal model of Alzheimer’s disease. J Pharmacol Sci 143(4):290–299
pubmed: 32507685
doi: 10.1016/j.jphs.2020.05.009
Leidgens V, Proske J, Rauer L, Moeckel S, Renner K, Bogdahn U, Riemenschneider MJ, Proescholdt M, Vollmann-Zwerenz A, Hau P, Seliger C (2017) Stattic and metformin inhibit brain tumor initiating cells by reducing STAT3-phosphorylation. Oncotarget 8(5):8250–8263. https://doi.org/10.18632/oncotarget.14159
doi: 10.18632/oncotarget.14159
pubmed: 28030813
Li SF, Ouyang BS, Zhao X, Wang YP. 2018 Analgesic effect of AG490, a Janus kinase inhibitor, on oxaliplatin-induced acute neuropathic pain. Neural Regen Res.;13(8):1471-1476. Erratum in: Neural Regen Res. 2019 Apr;14(4):612 https://doi.org/10.4103/1673-5374.235305
García-Bueno B, Madrigal JL, Lizasoain I, Moro MA, Lorenzo P, Leza JC (2005) Peroxisome proliferator-activated receptor gamma activation decreases neuroinflammation in brain after stress in rats. Biol Psychiatry 57(8):885–894. https://doi.org/10.1016/j.biopsych.2005.01.007
doi: 10.1016/j.biopsych.2005.01.007
pubmed: 15820709
García-Bueno B, Caso JR, Pérez-Nievas BG, Lorenzo P, Leza JC (2007) Effects of peroxisome proliferator-activated receptor gamma agonists on brain glucose and glutamate transporters after stress in rats. Neuropsychopharmacol 32(6):1251–1260
doi: 10.1038/sj.npp.1301252
Jahrling JB, Hernandez CM, Denner L, Dineley KT (2014) PPARγ recruitment to active ERK during memory consolidation is required for Alzheimer’s disease-related cognitive enhancement. J Neurosci 34(11):4054–4063. https://doi.org/10.1523/JNEUROSCI.4024-13.2014
doi: 10.1523/JNEUROSCI.4024-13.2014
pubmed: 24623782
pmcid: 3951699
Martinez AA, Morgese MG, Pisanu A, Macheda T, Paquette MA, Seillier A, Cassano T, Carta AR, Giuffrida A (2015) Activation of PPAR-gamma receptors reduces levodopa-induced dyskinesias in 6-OHDA-lesioned rats. NeurobiolDis 74:295–304. https://doi.org/10.1016/j.nbd.2014.11.024
doi: 10.1016/j.nbd.2014.11.024
Chamberlain S, Gabriel H, Strittmatter W, Didsbury J (2020) An exploratory phase IIa Study of the PPAR delta/gamma agonist T3D–959 assessing metabolic and cognitive function in subjects with mild to moderate Alzheimer’s disease. J Alzheimer’s Disease 73(3):1085–1103
doi: 10.3233/JAD-190864
Kielian T, Syed MM, Liu S, Phulwani NK, Phillips N, Wagoner G, Drew PD, Esen N (2008) The synthetic peroxisome proliferator-activated receptor-gamma agonist ciglitazone attenuates neuroinflammation and accelerates encapsulation in bacterial brain abscesses. J Immunol 180(7):5004–5016. https://doi.org/10.4049/jimmunol.180.7.5004
doi: 10.4049/jimmunol.180.7.5004
pubmed: 18354226
Seok H, Lee M, Shin E (2019) Low-dose pioglitazone can ameliorate learning and memory impairment in a mouse model of dementia by increasing LRP1 expression in the hippocampus. Sci Rep 9:4414. https://doi.org/10.1038/s41598-019-40736-x
doi: 10.1038/s41598-019-40736-x
pubmed: 30867485
pmcid: 6416325
Mirza R, Sharma B. 2019 A selective peroxisome proliferator-activated receptor-γ agonist benefited propionic acid induced autism-like behavioural phenotypes in rats by attenuation of neuroinflammation and oxidative stress. Chem
Z-J Liu Z-H Li L Liu W-X Tang Y Wang M-R Dong C Xiao 2016 Curcumin attenuates beta-amyloid-induced neuroinflammation via activation of peroxisome proliferator-activated receptor-gamma function in a rat model of Alzheimer’s disease Front Pharmacol 7 https://doi.org/10.3389/fphar.2016.00261
Weng Q-F, Chen G-B, Min-Guang Xu, Long R-T, Wang H, Wang X-Y, Jiang C-N, Yi X-N (2019) Upregulation of PPAR-gamma activity nhibits cyclooxygenase 2 expression in cortical neurons with N-methyl-d-aspartic acid induced excitatory neurotoxicity. Biotechnol Biotechnol Equip 33(1):1018–1023. https://doi.org/10.1080/13102818.2019.1634488
doi: 10.1080/13102818.2019.1634488
Katsouri L, Lim YM, Blondrath K, Eleftheriadou I, Lombardero L, Birch AM, Sastre M (2016) PPARγ-coactivator-1α gene transfer reduces neuronal loss and amyloid-β generation by reducing β-secretase in an Alzheimer’s disease model. Proc Natl Acad Sci 113(43):12292–12297. https://doi.org/10.1073/pnas.1606171113
doi: 10.1073/pnas.1606171113
pubmed: 27791018
pmcid: 5087021
Heneka MT, Klockgether T, Feinstein DL (2000) Peroxisome proliferator-activated receptor-gamma ligands reduce neuronal inducible nitric oxide synthase expression and cell death in vivo. Erratum In J Neurosci 2000 Nov 15 20(22) 20(18):6862–6867. https://doi.org/10.1523/JNEUROSCI.20-18-06862.2000
doi: 10.1523/JNEUROSCI.20-18-06862.2000
Wu XJ, Sun XH, Wang SW, Chen JL, Bi YH, Jiang DX (2018) Mifepristone alleviates cerebral ischemia-reperfusion injury in rats by stimulating PPAR γ. Eur Rev Med Pharmacol Sci 22(17):5688–5696. https://doi.org/10.26355/eurrev_201809_15836
doi: 10.26355/eurrev_201809_15836
pubmed: 30229846
Bhandari R, Kuhad A (2017) Resveratrol suppresses neuroinflammation in the experimental paradigm of autism spectrum disorders. Neurochem Int 103:8–23. https://doi.org/10.1016/j.neuint.2016.12.012
doi: 10.1016/j.neuint.2016.12.012
pubmed: 28025035
You, Y.-H. Qin Z.-Q., Zhang, H.-L. Yuan, Z.-H., & Yu X 2019 MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR. Bioscience Reports BSR20181904 https://doi.org/10.1042/bsr20181904
Masciopinto F, Di Pietro N, Corona C, Bomba M, Pipino C, Curcio M, Sensi SL (2012) Effects of long-term treatment with pioglitazone on cognition and glucose metabolism of PS1-KI, 3xTg-AD and wild-type mice. Cell Death Dis 3(12):e448–e448. https://doi.org/10.1038/cddis.2012.189
doi: 10.1038/cddis.2012.189
pubmed: 23254291
pmcid: 3542623
Mirza R, Sharma B (2019) Benefits of Fenofibrate in prenatal valproic acid-induced autism spectrum disorder related phenotype in rats. Brain Res Bull 147:36–46. https://doi.org/10.1016/j.brainresbull.2019.02.003
doi: 10.1016/j.brainresbull.2019.02.003
pubmed: 30769127