Signaling, polyubiquitination, trafficking, and inclusions: sequestosome 1/p62's role in neurodegenerative disease

Aggregated misfolded proteins are hallmarks of most neurodegenerative diseases. In a chronic disease state, including pathologic situations of oxidative stress, these proteins are sequestered into inclusions. Accumulation of aggregated proteins can be prevented by chaperones, or by targeting their d...

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Bibliographic Details
Published in:Journal of biomedicine & biotechnology 2006, Vol.2006 (3), p.62079-12
Main Authors: Wooten, Marie W, Hu, Xiao, Babu, J Ramesh, Seibenhener, M Lamar, Geetha, Thangiah, Paine, Michael G, Wooten, Michael C
Format: Article
Language:English
Subjects:
Degeneration
Nervous system
Protein folding
Review
Ubiquitin-proteasome system
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Summary:Aggregated misfolded proteins are hallmarks of most neurodegenerative diseases. In a chronic disease state, including pathologic situations of oxidative stress, these proteins are sequestered into inclusions. Accumulation of aggregated proteins can be prevented by chaperones, or by targeting their degradation to the UPS. If the accumulation of these proteins exceeds their degradation, they may impair the function of the proteasome. Alternatively, the function of the proteasome may be preserved by directing aggregated proteins to the autophagy-lysosome pathway for degradation. Sequestosome 1/p62 has recently been shown to interact with polyubiquitinated proteins through its UBA domain and may direct proteins to either the UPS or autophagosome. P62 is present in neuronal inclusions of individuals with Alzheimer's disease and other neurodegenerative diseases. Herein, we review p62's role in signaling, aggregation, and inclusion formation, and specifically as a possible contributor to Alzheimer's disease. The use of p62 as a potential target for the development of therapeutics and as a disease biomarker is also discussed.
ISSN:1110-7243
1110-7251
DOI:10.1155/JBB/2006/62079