Proteostasis in striatal cells and selective neurodegeneration in Huntington's disease

Julia Margulis; Steven Finkbeiner

doi:10.3389/fncel.2014.00218

Proteostasis in striatal cells and selective neurodegeneration in Huntington's disease

Front Cell Neurosci. 2014 Aug 7:8:218. doi: 10.3389/fncel.2014.00218. eCollection 2014.

Authors

Julia Margulis¹, Steven Finkbeiner²

Affiliations

¹ 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.
² 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.

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.

Keywords: Huntington’s disease; autophagy; proteasome; proteostasis; striatum.

Publication types

Review

Abstract

Publication types

Grants and funding