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Sci. Aging Knowl. Environ., 27 August 2003
Vol. 2003, Issue 34, p. re6
[DOI: 10.1126/sageke.2003.34.re6]


Ubiquitin, Proteasomes, and the Aging Brain

Douglas A. Gray, Maria Tsirigotis, and John Woulfe

Douglas A. Gray is at the Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada K1H 1C4 and the Ottawa Health Research Institute, Ottawa, Ontario, Canada K1Y 4E9. Maria Tsirigotis is at the Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada K1H 1C4. John Woulfe is at the Ottawa Health Research Institute, Ottawa, Ontario, Canada K1Y 4E9 and in the Department of Pathology, Ottawa Hospital, Ottawa, Canada K1Y 4E9. E-mail: Doug.Gray{at};2003/34/re6

Key Words: ubiquitin • proteasome • neurodegeneration

Abstract: Ubiquitinated proteinaceous inclusions are the hallmark of many neurodegenerative diseases. Inefficient proteolysis might lead to the accumulation and ultimate deposition of potentially toxic entities as inclusions within neurons or glial cells. This hypothesis is supported by genetic evidence both from patient populations and from engineered mutations in genes that encode ubiquitin/proteasome components in mice. The appearance of similar inclusions in the brains of elderly individuals of normal and subclinical conditions begs the question of whether there is a general age-related decline in the ability of the ubiquitin/proteasome pathway (UPP) to recognize and eliminate abnormal proteins, and whether such a decline would be reflected by changes in the abundance or activity of some or all components of the UPP. Here we describe alterations in the aging mammalian brain that correlate with a decline in the function of the UPP and review the evidence for age-related changes in specific UPP components. These alterations are discussed within the context of prevalent theories of aging.

Citation: D. A. Gray, M. Tsirigotis, J. Woulfe, Ubiquitin, Proteasomes, and the Aging Brain. Sci. SAGE KE 2003 (34), re6 (2003).

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