AUTHOR=Margulis Julia , Finkbeiner Steven 

TITLE=Proteostasis in striatal cells and selective neurodegeneration in Huntington’s disease

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=8

YEAR=2014

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2014.00218

DOI=10.3389/fncel.2014.00218

ISSN=1662-5102

ABSTRACT=<p>Selective neuronal loss is a hallmark of neurodegenerative diseases, including Huntington’s disease (HD). Although mutant huntingtin, the protein responsible for HD, is expressed ubiquitously, a subpopulation of neurons in the striatum is the first to succumb. In this review, we examine evidence that protein quality control pathways, including the ubiquitin proteasome system, autophagy, and chaperones, are significantly altered in striatal neurons. These alterations may increase the susceptibility of striatal neurons to mutant huntingtin-mediated toxicity. This novel view of HD pathogenesis has profound therapeutic implications: protein homeostasis pathways in the striatum may be valuable targets for treating HD and other misfolded protein disorders.</p>