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Volume 8, Pages 421-433
Review Article

The Ubiquitin-Proteasome Pathway in Huntington's Disease

1Gladstone Institute of Neurological Disease, 1650 Owens St., San Francisco, CA 94158, USA
2Medical Scientist Training Program, University of California, 533 Parnassus Ave, San Francisco, CA 94143, USA
3Departments of Neurology and Physiology, University of California, 533 Parnassus Ave., San Francisco, CA 94143, USA

Received 7 January 2008; Accepted 3 April 2008

Academic Editor: George Siegel

Copyright © 2008 Siddhartha Mitra and Steven Finkbeiner.


The accumulation of mutant protein is a common feature of neurodegenerative disease. In Huntington's disease, a polyglutamine expansion in the huntingtin protein triggers neuronal toxicity. Accompanying neuronal death, mutant huntingtin aggregates in large macromolecular structures called inclusion bodies. The function of the machinery for intracellular protein degradation is linked to huntingtin toxicity and components of this machinery colocalize with inclusion bodies. An increasing body of evidence implicates the ubiquitin-proteasome pathway in the failure of cells to degrade mutant huntingtin. A number of potential mechanisms that link compromised ubiquitin-proteasome pathway function and neurodegeneration have been proposed and may offer opportunities for therapeutic intervention.