Rosiglitazone Treatment Prevents Mitochondrial Dysfunction in Mutant Huntingtin-expressing Cells: POSSIBLE ROLE OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-γ (PPARγ) IN THE PATHOGENESIS OF HUNTINGTON DISEASE*

摘要: Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the PPAR family transcription factors. Synthetic PPARγ agonists are used as oral anti-hyperglycemic drugs for treatment non-insulin-dependent diabetes. However, emerging evidence indicates that activators can also prevent or attenuate neurodegeneration. Given these previous findings, focus this report on potential neuroprotective role activation in preventing loss mitochondrial function Huntington disease (HD). For studies we striatal cells express wild-type (STHdhQ7/Q7) mutant (STHdhQ111/Q111) huntingtin protein at physiological levels. Treatment with thapsigargin resulted significant decrease calcium uptake, an increase reactive oxygen species production, and membrane potential. by rosiglitazone prevented dysfunction oxidative stress occurred when were challenged pathological increases calcium. The beneficial effects likely mediated PPARγ, all protective antagonist GW9662. Additionally, signaling pathway was significantly impaired decreases expression reduced transcriptional activity. increased mass levels, suggesting cells. Altogether, attenuates huntingtin-expressing cells, could be important therapeutic avenue to ameliorate occurs HD.