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Targeting ER stress/ER stress response in myopathies

There is more skeletal muscle tissue in the body than any other tissue and, as it is the organ of the majority of metabolic activity, muscle defect can affect the health of the entire body. Endoplasmic reticulum (ER) stress due to defects in protein folding/degradation balance, altered calcium and l...

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Autor principal: Zito, Ester
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556854/
https://www.ncbi.nlm.nih.gov/pubmed/31181458
http://dx.doi.org/10.1016/j.redox.2019.101232
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author Zito, Ester
author_facet Zito, Ester
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description There is more skeletal muscle tissue in the body than any other tissue and, as it is the organ of the majority of metabolic activity, muscle defect can affect the health of the entire body. Endoplasmic reticulum (ER) stress due to defects in protein folding/degradation balance, altered calcium and lipid levels and alterations in ER-mitochondria contacts has recently been recognised as the pathogenic cause of many different myopathies. In addition, a maladaptive ER stress response triggered by ER stress and mediated by three ER stress sensors (PERK, IRE1 and ATF6) is involved in a failure to relieve muscle tissue from this stress. Targeting ER stress and the ER stress response pathway offers a broad range of opportunities for treating myopathies but, as the inhibition of the three ER stress sensors may not be safe because it could lead to unexpected effects; it therefore calls for careful analysis of the changes in downstream signal transduction in the different myopathies so these sub-pathways can be pharmacologically targeted. This review summarises the known inhibitors of the ER stress response and the successful results obtained using some of them in mouse models of muscle diseases caused by ER stress/ER stress response.
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spelling pubmed-65568542019-06-13 Targeting ER stress/ER stress response in myopathies Zito, Ester Redox Biol Mini Review There is more skeletal muscle tissue in the body than any other tissue and, as it is the organ of the majority of metabolic activity, muscle defect can affect the health of the entire body. Endoplasmic reticulum (ER) stress due to defects in protein folding/degradation balance, altered calcium and lipid levels and alterations in ER-mitochondria contacts has recently been recognised as the pathogenic cause of many different myopathies. In addition, a maladaptive ER stress response triggered by ER stress and mediated by three ER stress sensors (PERK, IRE1 and ATF6) is involved in a failure to relieve muscle tissue from this stress. Targeting ER stress and the ER stress response pathway offers a broad range of opportunities for treating myopathies but, as the inhibition of the three ER stress sensors may not be safe because it could lead to unexpected effects; it therefore calls for careful analysis of the changes in downstream signal transduction in the different myopathies so these sub-pathways can be pharmacologically targeted. This review summarises the known inhibitors of the ER stress response and the successful results obtained using some of them in mouse models of muscle diseases caused by ER stress/ER stress response. Elsevier 2019-06-04 /pmc/articles/PMC6556854/ /pubmed/31181458 http://dx.doi.org/10.1016/j.redox.2019.101232 Text en © 2019 Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Mini Review
Zito, Ester
Targeting ER stress/ER stress response in myopathies
title Targeting ER stress/ER stress response in myopathies
title_full Targeting ER stress/ER stress response in myopathies
title_fullStr Targeting ER stress/ER stress response in myopathies
title_full_unstemmed Targeting ER stress/ER stress response in myopathies
title_short Targeting ER stress/ER stress response in myopathies
title_sort targeting er stress/er stress response in myopathies
topic Mini Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556854/
https://www.ncbi.nlm.nih.gov/pubmed/31181458
http://dx.doi.org/10.1016/j.redox.2019.101232
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