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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Review Article| October 01 2005
The ubiquitin–proteasome system and neurodegenerative disorders
Robert Layfield ;
James Lowe ;
Essays Biochem (2005) 41: 157–171.
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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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