Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity
Chaperones and co-chaperones enable protein folding and degradation, safeguarding the proteome against proteotoxic stress. Chaperones display dynamic responses to exogenous and endogenous stressors and thus constitute a key component of the proteostasis network (PN), an intricately regulated network...
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The Company of Biologists
2016-08-01
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doaj-6e589602af2048ed8899fbe4ca3432ab2020-11-24T21:57:43ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112016-08-019882383810.1242/dmm.024703024703Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicityMarc Brehme0Cindy Voisine1 Joint Research Center for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, 52062 Aachen, Germany Department of Biology, Northeastern Illinois University, Chicago, IL 60625, USA Chaperones and co-chaperones enable protein folding and degradation, safeguarding the proteome against proteotoxic stress. Chaperones display dynamic responses to exogenous and endogenous stressors and thus constitute a key component of the proteostasis network (PN), an intricately regulated network of quality control and repair pathways that cooperate to maintain cellular proteostasis. It has been hypothesized that aging leads to chronic stress on the proteome and that this could underlie many age-associated diseases such as neurodegeneration. Understanding the dynamics of chaperone function during aging and disease-related proteotoxic stress could reveal specific chaperone systems that fail to respond to protein misfolding. Through the use of suppressor and enhancer screens, key chaperones crucial for proteostasis maintenance have been identified in model organisms that express misfolded disease-related proteins. This review provides a literature-based analysis of these genetic studies and highlights prominent chaperone modifiers of proteotoxicity, which include the HSP70-HSP40 machine and small HSPs. Taken together, these studies in model systems can inform strategies for therapeutic regulation of chaperone functionality, to manage aging-related proteotoxic stress and to delay the onset of neurodegenerative diseases.http://dmm.biologists.org/content/9/8/823ChaperoneCo-chaperoneChaperomeProteostasis networkProtein-misfolding diseaseDisease models |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marc Brehme Cindy Voisine |
spellingShingle |
Marc Brehme Cindy Voisine Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity Disease Models & Mechanisms Chaperone Co-chaperone Chaperome Proteostasis network Protein-misfolding disease Disease models |
author_facet |
Marc Brehme Cindy Voisine |
author_sort |
Marc Brehme |
title |
Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity |
title_short |
Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity |
title_full |
Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity |
title_fullStr |
Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity |
title_full_unstemmed |
Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity |
title_sort |
model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity |
publisher |
The Company of Biologists |
series |
Disease Models & Mechanisms |
issn |
1754-8403 1754-8411 |
publishDate |
2016-08-01 |
description |
Chaperones and co-chaperones enable protein folding and degradation, safeguarding the proteome against proteotoxic stress. Chaperones display dynamic responses to exogenous and endogenous stressors and thus constitute a key component of the proteostasis network (PN), an intricately regulated network of quality control and repair pathways that cooperate to maintain cellular proteostasis. It has been hypothesized that aging leads to chronic stress on the proteome and that this could underlie many age-associated diseases such as neurodegeneration. Understanding the dynamics of chaperone function during aging and disease-related proteotoxic stress could reveal specific chaperone systems that fail to respond to protein misfolding. Through the use of suppressor and enhancer screens, key chaperones crucial for proteostasis maintenance have been identified in model organisms that express misfolded disease-related proteins. This review provides a literature-based analysis of these genetic studies and highlights prominent chaperone modifiers of proteotoxicity, which include the HSP70-HSP40 machine and small HSPs. Taken together, these studies in model systems can inform strategies for therapeutic regulation of chaperone functionality, to manage aging-related proteotoxic stress and to delay the onset of neurodegenerative diseases. |
topic |
Chaperone Co-chaperone Chaperome Proteostasis network Protein-misfolding disease Disease models |
url |
http://dmm.biologists.org/content/9/8/823 |
work_keys_str_mv |
AT marcbrehme modelsystemsofproteinmisfoldingdiseasesrevealchaperonemodifiersofproteotoxicity AT cindyvoisine modelsystemsofproteinmisfoldingdiseasesrevealchaperonemodifiersofproteotoxicity |
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1725853966102691840 |