Pharmacological upregulation of PGC1α in oligodendrocytes: implications for Huntington's Disease.

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.