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.
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October 2005
Issue Editors
Review Article|
October 01 2005
The ubiquitin–proteasome system and neurodegenerative disorders
Robert Layfield
;
Robert Layfield
1
*School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, U.K.
1To whom correspondence should be addressed (email robert.layfield@nottingham.ac.uk).
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James Lowe
;
James Lowe
†School of Molecular Medical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, U.K.
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Lynn Bedford
Lynn Bedford
*School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, U.K.
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Essays Biochem (2005) 41: 157–171.
Citation
John Mayer, Robert Layfield, Robert Layfield, James Lowe, Lynn Bedford; The ubiquitin–proteasome system and neurodegenerative disorders. Essays Biochem 1 October 2005; 41 157–171. doi: https://doi.org/10.1042/bse0410157
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