Mechanisms of protein homeostasis in health, aging and disease.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_A94A5927B9DC
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
Mechanisms of protein homeostasis in health, aging and disease.
Journal
Swiss Medical Weekly
Author(s)
Goloubinoff P.
ISSN
1424-3997 (Electronic)
ISSN-L
0036-7672
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
146
Pages
w14306
Language
english
Notes
Publication types: Journal Article Publication Status: epublish
Abstract
When emerging from the ribosomes, new polypeptides need to fold properly, eventually translocate, and then assemble into stable, yet functionally flexible complexes. During their lifetime, native proteins are often exposed to stresses that can partially unfold and convert them into stably misfolded and aggregated species, which can in turn cause cellular damage and propagate to other cells. In animal cells, especially in aged neurons, toxic aggregates may accumulate, induce cell death and lead to tissue degeneration via different mechanisms, such as apoptosis as in Parkinson's and Alzheimer's diseases and aging in general. The main cellular mechanisms effectively controlling protein homeostasis in youth and healthy adulthood are: (1) the molecular chaperones, acting as aggregate unfolding and refolding enzymes, (2) the chaperone-gated proteases, acting as aggregate unfolding and degrading enzymes, (3) the aggresomes, acting as aggregate compacting machineries, and (4) the autophagosomes, acting as aggregate degrading organelles. For unclear reasons, these cellular defences become gradually incapacitated with age, leading to the onset of degenerative diseases. Understanding these mechanisms and the reasons for their incapacitation in late adulthood is key to the design of new therapies against the progression of aging, degenerative diseases and cancers.
Pubmed
Web of science
Open Access
Yes
Create date
14/04/2016 17:28
Last modification date
20/08/2019 16:13
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