| Aging and regulated protein degradation: who has the UPPer hand? | |
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MedLine Citation:
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PMID: 17681036 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In all cells, protein degradation is a constant, ongoing process that is critical for cell survival and repair. The ubiquitin/proteasome pathway (UPP) is the major proteolytic pathway that degrades intracellular proteins in a regulated manner. It plays critical roles in many cellular processes and diseases. Disruption of the UPP is particularly relevant to pathophysiological conditions that provoke the accumulation of aberrant proteins, such as in aging as well as in a variety of neurodegenerative disorders including Alzheimer's and Parkinson's diseases. For unknown reasons, most of these neurodegenerative disorders that include familial and sporadic cases exhibit a late onset. It is possible that these neurodegenerative conditions exhibit a late onset because proteasome activity decreases with aging. Aging-dependent impairment in proteolysis mediated by the proteasome may have profound ramifications for cell viability. It can lead to the accumulation of modified, potentially toxic proteins in cells and can cause cell injury or premature cell death by apoptosis or necrosis. While it is accepted that aging affects UPP function, the question is why does aging cause a decline in regulated protein degradation by the UPP? Herein, we review some of the properties of the UPP and mechanisms mediating its age-dependent impairment. We also discuss the relevance of these findings leading to a model that proposes that UPP dysfunction may be one of the milestones of aging. |
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Authors:
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Vita A Vernace; Thomas Schmidt-Glenewinkel; Maria E Figueiredo-Pereira |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review Date: 2007-08-06 |
Journal Detail:
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Title: Aging cell Volume: 6 ISSN: 1474-9718 ISO Abbreviation: Aging Cell Publication Date: 2007 Oct |
Date Detail:
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Created Date: 2007-09-18 Completed Date: 2007-12-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101130839 Medline TA: Aging Cell Country: England |
Other Details:
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Languages: eng Pagination: 599-606 Citation Subset: IM |
Affiliation:
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Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10021, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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metabolism* Animals Humans Proteasome Endopeptidase Complex / metabolism* Proteins / metabolism* Ubiquitin / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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GM60654/GM/NIGMS NIH HHS; NS41073/NS/NINDS NIH HHS; RR03037/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Proteins; 0/Ubiquitin; EC 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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