The aggravating role of the ubiquitin-proteasome system in neurodegeneration.
Association of protein inclusions or aggregates within brain tissues of patients with neurodegenerative disorders has been widely reported. These inclusions are commonly characterised both by the presence of ubiquitylated proteins and the sequestration of components of the ubiquitin-proteasome system (UPS). Such observations have led to the proposition that the UPS has a direct role in their formation. Indeed, the presence of ubiquitylated proteins and UPS components in inclusions may reflect unsuccessful attempts by the UPS to remove aggregating proteins. Whether the physical presence of inclusions causes cell death or, conversely, whether they are non-toxic and their presence reflects a cellular protective mechanism remains highly controversial.
Ardley
Helen C
HC
Molecular Medicine Unit, University of Leeds, St. James's University Hospital, Leeds LS9 7TF, UK. h.c.ardley@leeds.ac.uk
Hung
Chao-Chun
CC
Robinson
Philip A
PA
D006801:Humans; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex