Neuroprotection in Huntington’s Disease via Transcriptional Modification
Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder characterized by motor cognitive dysfunction. Mitochondrial dysfunction and metabolic deficits are implicated in the pathophysiology of neurodegenerative diseases such as Parkinson's disease and HD and have been linked to the transcriptional dysregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a). Of the members of the PPAR family of transcription factors which require co-activation by PCG-1a, PPAR delta is the most ubiquitous and abundant in the central nervous system. Previous studies have demonstrated that PPAR-delta is dysregulated in HD leading to impairment of mitochondrial function. Furthermore, activation of the PPAR-delta pathway provided neuroprotective effects in HD models, implicating this pathway as an important therapeutic target for HD. The purpose of this study was to investigate the hypothesis that neuroprotection imparted by Bexarotene in vitro is mediated by the PPAR-delta pathway.