Protein Aggregation and Neurodegeneration: Clues from a Yeast Model of Huntington’s Disease

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N. Bocharova¹, R. Chave-Cox², S. Sokolov¹, D. Knorre³, and F. Severin^3*

¹Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-4195; E-mail: bona@genebee.msu.ru

²University College London, 20 Gordon Street, London WC1H 0AJ United Kingdom; fax: +44 (0) 20-7679-7463; E-mail: r.chave-cox@ucl.ac.uk

³Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-3181; E-mail: severin@genebee.msu.ru

^* To whom correspondence should be addressed.

Received May 29, 2008; Revision received July 30, 2008

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A number of neurodegenerative diseases are accompanied by the appearance of intracellular protein aggregates. Huntington’s disease (HD) is caused by a mutation in a gene encoding huntingtin. The mutation causes the expansion of the polyglutamine (polyQ) domain and consequently polyQ-containing aggregates accumulate and neurons in the striatum die. The role of the aggregates is still not clear: they may be the cause of cytotoxicity or a manifestation of the cellular attempt to remove the misfolded proteins. There is accumulating evidence that the main cause of HD is the interaction of the mutated huntingtin with other polyQ-containing proteins and molecular chaperones and most studies based on a yeast model of HD support this point of view. Data obtained using yeasts suggest pathological consequences of polyQ–proteasomal interaction: proteasomal overload by polyQs may interfere with functions of the cell cycle-regulating proteins.

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KEY WORDS: Huntington’s disease, aggregation, polyglutamine, yeast

DOI: 10.1134/S0006297909020163

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