2University College London, 20 Gordon Street, London WC1H 0AJ United Kingdom; fax: +44 (0) 20-7679-7463; E-mail: firstname.lastname@example.org
3Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-3181; E-mail: email@example.com
* To whom correspondence should be addressed.
Received May 29, 2008; Revision received July 30, 2008
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.
KEY WORDS: Huntington’s disease, aggregation, polyglutamine, yeast