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Protein aggregation and neurodegeneration: Clues from a yeast model of Huntington’s disease

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Abstract

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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Abbreviations

APC:

anaphase-promoting complex

HD:

Huntington’s disease

polyQ:

polyglutamine

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Author information

Authors and Affiliations

  1. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992, Moscow, Russia

    N. Bocharova & S. Sokolov

  2. University College London, 20 Gordon Street, London, WC1H 0AJ, UK

    R. Chave-Cox

  3. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Moscow, Russia

    D. Knorre & F. Severin

Authors
  1. N. Bocharova
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  2. R. Chave-Cox
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  3. S. Sokolov
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  4. D. Knorre
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  5. F. Severin
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Corresponding author

Correspondence to F. Severin.

Additional information

Published in Russian in Biokhimiya, 2009, Vol. 74, No. 2, pp. 284–288.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM08-184, December 14, 2008.

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Bocharova, N., Chave-Cox, R., Sokolov, S. et al. Protein aggregation and neurodegeneration: Clues from a yeast model of Huntington’s disease. Biochemistry Moscow 74, 231–234 (2009). https://doi.org/10.1134/S0006297909020163

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  • DOI: https://doi.org/10.1134/S0006297909020163

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