title: Proteostasis in striatal cells and selective neurodegeneration in Huntington's disease.
abstract: 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.
authors.affiliation: Gladstone Institute of Neurological Disease, J. David Gladstone Institutes San Francisco, CA, USA ; Department of Neurology, University of California at San Francisco San Francisco, CA, USA ; Department of Physiology, University of California at San Francisco San Francisco, CA, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Margulis
authors.affiliation: Gladstone Institute of Neurological Disease, J. David Gladstone Institutes San Francisco, CA, USA ; Department of Neurology, University of California at San Francisco San Francisco, CA, USA ; Department of Physiology, University of California at San Francisco San Francisco, CA, USA ; Taube/Koret Center for Huntington's Disease Research San Francisco, CA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Finkbeiner
keywords: Huntington’s disease; autophagy; proteasome; proteostasis; striatum