A role for autophagy in Huntington's disease.

The lysosome-mediated degradation pathway known as macroautophagy is the most versatile means through which cells can eliminate and recycle unwanted materials. Through both selective and non-selective means, macroautophagy can degrade a wide range of cargoes from bulk cytosol to organelles and aggregated proteins. Although studies of disorders such as Parkinson's disease and Amyotrophic Lateral Sclerosis suggest that autophagic and lysosomal dysfunction directly contributes to disease, this had not been the case for the polyglutamine disorder Huntington's disease (HD), for which there was little indication of a disruption in the autophagic-lysosomal system. This supported the possibility of targeting autophagy as a much needed therapeutic approach to combat this disease. Possibly challenging this view, however, are a recent set of studies suggesting that the protein affected in Huntington's disease, huntingtin, might mechanistically contribute to macroautophagy. In this review, we will explore how autophagy might impact or be impacted by HD pathogenesis, and whether a therapeutic approach centering on autophagy may be possible for this yet incurable disease.