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PMID: 20732422 Published · ppublish English Journal Article Review

The elimination of accumulated and aggregated proteins: a role for aggrephagy in neurodegeneration.

Neurobiology of disease ·Vol. 43 ·No. 1 ·2011-07-00 ·Pages 17-28

Yamamoto A, Simonsen A

Abstract

The presence of ubiquitinated protein inclusions is a hallmark of most adult onset neurodegenerative disorders. Although the toxicity of these structures remains controversial, their prolonged presence in neurons is indicative of some failure in fundamental cellular processes. It therefore may be possible that driving the elimination of inclusions can help re-establish normal cellular function. There is growing evidence that macroautophagy has two roles; first, as a non-selective degradative response to cellular stress such as starvation, and the other as a highly selective quality control mechanism whose basal levels are important to maintain cellular health. One particular form of macroautophagy, aggrephagy, may have particular relevance in neurodegeneration, as it is responsible for the selective elimination of accumulated and aggregated ubiquitinated proteins. In this review, we will discuss the molecular mechanisms and role of protein aggregation in neurodegeneration, as well as the molecular mechanism of aggrephagy and how it may impact disease. This article is part of a Special Issue entitled "Autophagy and protein degradation in neurological diseases."

MeSH Terms
Autophagy/physiology Humans Nerve Degeneration/metabolism,pathology Neurodegenerative Diseases/metabolism,pathology Neurons/metabolism,pathology Proteins/metabolism Ubiquitination/physiology
Chemicals
Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Yamamoto Ai
Dept of Neurology, Columbia University, New York, NY 10032, USA. ay46@columbia.edu
Simonsen Anne
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Article Info
Journal
Neurobiology of disease
Abbr.
Neurobiol Dis
ISSN
1095-953X
DOI
10.1016/j.nbd.2010.08.015
Email
ay46@columbia.edu
Published
2011-07-00
Epub
2010-00-20
Pages
17-28
Language
English
Region
United States
NLM ID
9500169
PMCID
PMC2998573
Subset
IM
Grants
NINDS NIH HHS · R01 NS050199 · United States
NINDS NIH HHS · R01 NS050199-06 · United States
NINDS NIH HHS · R01 NS063973 · United States
NINDS NIH HHS · R01 NS063973-04 · United States
External Links
PubMed source DOI: 10.1016/j.nbd.2010.08.015 PMC Full Text View journal details
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