title: The ubiquitin-proteasome system and neurodegenerative disorders.
abstract: As in all other mammalian tissues, the UPS (ubiquitin-proteasome system) is fundamental to normal brain function. A consistent feature of the major human neurodegenerative disorders is the accumulation of disease-related proteins, in non-native conformations, as protein aggregates within neurons or glial cells. Often the proteins in these aggregates are post-translationally conjugated with ubiquitin, suggesting a possible link between pathological protein-aggregation events in the nervous system and dysfunction of the UPS. Genetic evidence clearly demonstrates that disruption of ubiquitin-mediated processes can lead to neurodegeneration; however, the relationship between the UPS and idiopathic neurodegenerative disorders is less clear. In the latter cases, although a number of different mechanisms could potentially contribute to dysfunction of the UPS and promote the neurodegenerative process, whether UPS dysfunction is causally related to disease pathogenesis, or alternatively arises as a result of the pathological state, and indeed whether ubiquitinated inclusions are harmful or beneficial to cells, remains to be clarified.
authors.affiliation: School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK. robert.layfield@nottingham.ac.uk
authors.forename: Robert
authors.initials: R
authors.lastname: Layfield
authors.forename: James
authors.initials: J
authors.lastname: Lowe
authors.forename: Lynn
authors.initials: L
authors.lastname: Bedford
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex