title: Pharmacological upregulation of PGC1α in oligodendrocytes: implications for Huntington's Disease.
abstract: The coactivator PGC1α plays a role in the transcriptional regulation of energy metabolism and its deficiency has been implicated in abnormalities of myelination and oligodendrocyte differentiation in Huntington's disease (HD). In an effort to activate PGC1α in oligodendrocytes, we found that overexpression of SIRT1 or treatment with resveratrol (RSV) and SRT1720 upregulated PGC1α expression and increased oligodendrocyte differentiation. Interestingly, in oligodendrocytes expressing mutant huntingtin, SRT1720 but not RSV was able to restore PGC1α expression and the differentiation. These results suggest that pharmacological activation of PGC1α in oligodendrocytes by SRT1720 may provide a therapeutic opportunity for correction of deficient myelination in HD.
authors: MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors: Zhongmin
authors: Z
authors: Xiang
authors: MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors: Dimitri
authors: D
authors: Krainc
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006816:Huntington Disease / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077185:Resveratrol; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C525422:SRT1720; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D013267:Stilbenes; D014157:Transcription Factors; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: Huntington's disease; Oligodendrocyte; PGC1α; SIRT1; differentiation; resveratrol