Protein aggregation and neurodegeneration: clues from a yeast model of Huntington's disease.
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.
Bocharova
N
N
Lomonosov Moscow State University, Russia. bona@genebee.msu.ru
Chave-Cox
R
R
Sokolov
S
S
Knorre
D
D
Severin
F
F
D018797:Cell Cycle Proteins / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018832:Molecular Chaperones / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine; D046988:Proteasome Endopeptidase Complex