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PMID: 17047309 Published · ppublish English Journal Article

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

Journal of biomedicine & biotechnology ·Vol. 2006 ·No. 3 ·2006-00-00 ·Pages 62079

Wooten MW, Hu X, Babu JR, Seibenhener ML, Geetha T, Paine MG, Wooten MC

Abstract

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.

Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wooten Marie W
Program in Cell & Molecular Biosciences, Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA.
Hu Xiao
Babu J Ramesh
Seibenhener M Lamar
Geetha Thangiah
Paine Michael G
Wooten Michael C
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Article Info
Journal
Journal of biomedicine & biotechnology
Abbr.
J Biomed Biotechnol
ISSN
1110-7243
DOI
10.1155/JBB/2006/62079
Published
2006-00-00
Pages
62079
Language
English
Region
United States
NLM ID
101135740
PMCID
PMC1559922
Grants
NINDS NIH HHS · R01 NS033661 · United States
External Links
PubMed source DOI: 10.1155/JBB/2006/62079 PMC Full Text View journal details
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