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Exploiting Yeast Genetics to Inform Therapeutic Strategies for Huntington’s Disease

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Yeast Functional Genomics and Proteomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 548))

Summary

Huntington’s disease (HD) is a devastating neurodegenerative disorder that is inherited in an autosomal dominant fashion and is caused by a polyglutamine expansion in the protein huntingtin (htt). In recent years, modeling of various aspects of HD in the yeast Saccharomyces cerevisiae has provided insight into the conserved mechanisms of mutant htt toxicity in eukaryotic cells. The high degree of conservation of cellular and molecular processes between yeast and mammalian cells have made it a valuable system for studying basic mechanisms underlying human disease. Yeast models of HD recapitulate conserved disease-relevant phenotypes and can be used for drug discovery efforts as well as to gain mechanistic and genetic insights into candidate drugs. Here we provide a detailed overview of yeast models of mutant htt misfolding and toxicity and the molecular and phenotypic characterization of these models. We also review how these models identified novel therapeutic targets and compounds for HD and discuss the benefits and limitations of this model genetic system. Finally, we discuss how yeast may be used to provide further insight into the molecular and cellular mechanisms underlying HD and treatment strategies for this devastating disorder.

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Authors and Affiliations

  1. Gladstone Institute of Neurological Disease, Departments of Biochemistry and Biophysics, and Neurology, University of California, San Francisco, 1650 Owens St, San Francisco, CA, 94158, USA

    Flaviano Giorgini & Paul J. Muchowski

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  1. Flaviano Giorgini
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  2. Paul J. Muchowski
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Correspondence to Paul J. Muchowski .

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    © 2009 Humana Press, a part of Springer Science+Business Media, LLC

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    Giorgini, F., Muchowski, P.J. (2009). Exploiting Yeast Genetics to Inform Therapeutic Strategies for Huntington’s Disease. In: Stagljar, I. (eds) Yeast Functional Genomics and Proteomics. Methods in Molecular Biology, vol 548. Humana Press. https://doi.org/10.1007/978-1-59745-540-4_9

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    • DOI: https://doi.org/10.1007/978-1-59745-540-4_9

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    • Publisher Name: Humana Press

    • Print ISBN: 978-1-934115-71-8

    • Online ISBN: 978-1-59745-540-4

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