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Molecular and pharmacological chaperones for SOD1
The efficacy of superoxide dismutase-1 (SOD1) folding impacts neuronal loss in motor system neurodegenerative diseases. Mutations can prevent SOD1 post-translational processing leading to misfolding and cytoplasmic aggregation in familial amyotrophic lateral sclerosis (ALS). Evidence of immature, wi...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Portland Press Ltd.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458393/ https://www.ncbi.nlm.nih.gov/pubmed/32794552 http://dx.doi.org/10.1042/BST20200318 |
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author | Wright, Gareth S.A. |
author_facet | Wright, Gareth S.A. |
author_sort | Wright, Gareth S.A. |
collection | PubMed |
description | The efficacy of superoxide dismutase-1 (SOD1) folding impacts neuronal loss in motor system neurodegenerative diseases. Mutations can prevent SOD1 post-translational processing leading to misfolding and cytoplasmic aggregation in familial amyotrophic lateral sclerosis (ALS). Evidence of immature, wild-type SOD1 misfolding has also been observed in sporadic ALS, non-SOD1 familial ALS and Parkinson's disease. The copper chaperone for SOD1 (hCCS) is a dedicated and specific chaperone that assists SOD1 folding and maturation to produce the active enzyme. Misfolded or misfolding prone SOD1 also interacts with heat shock proteins and macrophage migration inhibitory factor to aid folding, refolding or degradation. Recognition of specific SOD1 structures by the molecular chaperone network and timely dissociation of SOD1-chaperone complexes are, therefore, important steps in SOD1 processing. Harnessing these interactions for therapeutic benefit is actively pursued as is the modulation of SOD1 behaviour with pharmacological and peptide chaperones. This review highlights the structural and mechanistic aspects of a selection of SOD1-chaperone interactions together with their impact on disease models. |
format | Online Article Text |
id | pubmed-7458393 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74583932020-09-04 Molecular and pharmacological chaperones for SOD1 Wright, Gareth S.A. Biochem Soc Trans Review Articles The efficacy of superoxide dismutase-1 (SOD1) folding impacts neuronal loss in motor system neurodegenerative diseases. Mutations can prevent SOD1 post-translational processing leading to misfolding and cytoplasmic aggregation in familial amyotrophic lateral sclerosis (ALS). Evidence of immature, wild-type SOD1 misfolding has also been observed in sporadic ALS, non-SOD1 familial ALS and Parkinson's disease. The copper chaperone for SOD1 (hCCS) is a dedicated and specific chaperone that assists SOD1 folding and maturation to produce the active enzyme. Misfolded or misfolding prone SOD1 also interacts with heat shock proteins and macrophage migration inhibitory factor to aid folding, refolding or degradation. Recognition of specific SOD1 structures by the molecular chaperone network and timely dissociation of SOD1-chaperone complexes are, therefore, important steps in SOD1 processing. Harnessing these interactions for therapeutic benefit is actively pursued as is the modulation of SOD1 behaviour with pharmacological and peptide chaperones. This review highlights the structural and mechanistic aspects of a selection of SOD1-chaperone interactions together with their impact on disease models. Portland Press Ltd. 2020-08-28 2020-08-14 /pmc/articles/PMC7458393/ /pubmed/32794552 http://dx.doi.org/10.1042/BST20200318 Text en © 2020 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . Open access for this article was enabled by the participation of University of Liverpool in an all-inclusive Read & Publish pilot with Portland Press and the Biochemical Society under a transformative agreement with JISC |
spellingShingle | Review Articles Wright, Gareth S.A. Molecular and pharmacological chaperones for SOD1 |
title | Molecular and pharmacological chaperones for SOD1 |
title_full | Molecular and pharmacological chaperones for SOD1 |
title_fullStr | Molecular and pharmacological chaperones for SOD1 |
title_full_unstemmed | Molecular and pharmacological chaperones for SOD1 |
title_short | Molecular and pharmacological chaperones for SOD1 |
title_sort | molecular and pharmacological chaperones for sod1 |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458393/ https://www.ncbi.nlm.nih.gov/pubmed/32794552 http://dx.doi.org/10.1042/BST20200318 |
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