Recent advances in understanding the pathogenesis of polyglutamine diseases: involvement of molecular chaperones and ubiquitin-proteasome pathway.
Polyglutamine diseases consist of a group of familial neurodegenerative disorders caused by expression of proteins containing expanded polyglutamine stretch. Over the past several years, tremendous progress has been made in identifying the molecular mechanisms by which the expanded polyglutamine tract leads to neuronal dysfunction and neurodegeneration. A common feature of most polyglutamine disorders is the occurrence of ubiquitin-positive neuronal intranuclear inclusions. The appearance of ubiquitinated aggregates implies an underline incapability of the cellular chaperones and proteasome machinery that normally functions to prevent the accumulation of misfolded proteins. Here we review the recent studies that have revealed a critical role for molecular chaperones and ubiquitin-proteasome pathway in the pathogenesis of polyglutamine diseases.
Jana
Nihar Ranjan
NR
National Brain Research Centre, SCO 5, 6 and 7, Sector 15, Part-II, 122 001 Gurgaon, India. nihar@nbrc.ac.in
Nukina
Nobuyuki
N
D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology; D010455:Peptides / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D010455:Peptides; D025801:Ubiquitin; C097188:polyglutamine; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex