Nature and cause of mitochondrial dysfunction in Huntington's disease: focusing on huntingtin and the striatum.

摘要: Polyglutamine expansion mutation in huntingtin causes Huntington's disease (HD). How mutant (mHtt) preferentially kills striatal neurons remains unknown. The link between mitochondrial dysfunction and HD pathogenesis stemmed from postmortem brain data toxin models. Current evidence genetic models, containing mHtt, supports with yet uncertain nature cause. Because mitochondria composition function varies across tissues cell-types, vulnerable may have distinctive features. This review focuses on mHtt the striatum, integrating experimental patients, mice, primary cultures cell-lines. I address (specific deficits) cause (mechanisms linked to mHtt) of dysfunction, considering limitations isolated vs. situ approaches, complications introduced by glia glycolysis cell-culture studies. relegates respiratory chain impairment a late secondary event. Upstream events include defective calcium handling, ATP production trafficking. Also, transcription abnormalities affecting composition, reduced trafficking synapses, direct interference structures enriched neurons, are possible mechanisms which amplifies vulnerability. Insights common neurodegenerative disorders selective vulnerability (Alzheimer's Parkinson's diseases) also addressed.