Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8842179 | Progress in Neurobiology | 2018 | 75 Pages |
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) is a widely expressed ligand-modulated transcription factor that governs the expression of genes involved in inflammation, redox equilibrium, trophic factor production, insulin sensitivity, and the metabolism of lipids and glucose. Synthetic PPARγ agonists (e.g. thiazolidinediones) are used to treat Type II diabetes and have the potential to limit the risk of developing brain injuries such as stroke by mitigating the influence of comorbidities. If brain injury develops, PPARγ serves as a master gatekeeper of cytoprotective stress responses, improving the chances of cellular survival and recovery of homeostatic equilibrium. In the acute injury phase, PPARγ directly restricts tissue damage by inhibiting the NFκB pathway to mitigate inflammation and stimulating the Nrf2/ARE axis to neutralize oxidative stress. During the chronic phase of acute brain injuries, PPARγ activation in injured cells culminates in the repair of gray and white matter, preservation of the blood-brain barrier, reconstruction of the neurovascular unit, resolution of inflammation, and long-term functional recovery. Thus, PPARγ lies at the apex of cell fate decisions and exerts profound effects on the chronic progression of acute injury conditions. Here, we review the therapeutic potential of PPARγ in stroke and brain trauma and highlight the novel role of PPARγ in long-term tissue repair. We describe its structure and function and identify the genes that it targets. PPARγ regulation of inflammation, metabolism, cell fate (proliferation/differentiation/maturation/survival), and many other processes also has relevance to other neurological diseases. Therefore, PPARγ is an attractive target for therapies against a number of progressive neurological disorders.
Keywords
CDKLPSCOXIGFMCPNCoRCTLNSCGFAPMBPGFPNrf2HDACiNOSPPARHspAMPAOPCADPEAENGFOGDNMDAMCAOCCIHDL-CSGZSVZTGFNPCSAHα-amino-3-hydroxy-5-methylisoxazole-4-propionic acidN-methyl-d-aspartic acidRetinoid X receptorPMN15d-PGJ2RXRRGZTBI15(S)-hydroxyeicosatetraenoic acidFDApGzTGZ15(S)-HETEBDNFGLTNOxTAIROSAtherosclerosisadenosine diphosphateTraumatic axonal injuryTraumatic brain injurySpinal cord injurycyclooxygenaseencephalomyelitisPPREmiddle cerebral artery occlusioninterferonIFNinterleukintransforming growth factorGlutamate transporterintracerebral hemorrhageSubarachnoid hemorrhageCNSDiabetes mellitusrosiglitazoneFood and Drug AdministrationSODBBBDendritic cellNeural stem celloligodendrocyte precursor cellneural progenitor cellAgeinducible nitric oxide synthaseSuperoxide dismutaseCMVcytomegaloviruscentral nervous systemCiglitazonenuclear factorsciantioxidant response elementperoxisome proliferator response elementnerve growth factorInsulin-like growth factorBrain-derived neurotrophic factornuclear factor erythroid 2-related factor 2cytotoxic T lymphocyteGalactose-specific lectinLow-density lipoproteinLDLlipopolysaccharideBlood-brain barrierOxygen-glucose deprivationICHsubgranular zonesubventricular zonepolymorphonuclear neutrophilnicotinamide adenine dinucleotide phosphate oxidaseAREnuclear receptor corepressorhistone deacetylasemonocyte chemotactic proteinGlial fibrillary acidic proteinHeat shock proteingreen fluorescent proteinMyelin basic proteinHigh-density lipoprotein-cholesterolcontrolled cortical impactcyclin-dependent kinasegalectinPioglitazoneReactive oxygen speciesperoxisome proliferator-activated receptor
Related Topics
Life Sciences
Neuroscience
Neuroscience (General)
Authors
Wei Cai, Tuo Yang, Huan Liu, Lijuan Han, Kai Zhang, Xiaoming Hu, Xuejing Zhang, Ke-Jie Yin, Yanqin Gao, Michael V.L. Bennett, Rehana K. Leak, Jun Chen,