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Skeletal Muscle Modulates Huntington’s Disease Pathogenesis in Mice: Role of Physical Exercise

Huntington’s disease (HD) is a monogenic fatal neurodegenerative disorder. However, there is increasing evidence that HD is a pleiotropic systemic disorder. In particular, skeletal muscle metabolism is greatly affected in HD, which in turn can have a major impact on whole-body metabolism and energet...

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Detalles Bibliográficos
Autores principales: Corrochano, Silvia, Blanco, Gonzalo, Acevedo-Arozena, Abraham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210627/
https://www.ncbi.nlm.nih.gov/pubmed/30397387
http://dx.doi.org/10.1177/1179069518809059
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author Corrochano, Silvia
Blanco, Gonzalo
Acevedo-Arozena, Abraham
author_facet Corrochano, Silvia
Blanco, Gonzalo
Acevedo-Arozena, Abraham
author_sort Corrochano, Silvia
collection PubMed
description Huntington’s disease (HD) is a monogenic fatal neurodegenerative disorder. However, there is increasing evidence that HD is a pleiotropic systemic disorder. In particular, skeletal muscle metabolism is greatly affected in HD, which in turn can have a major impact on whole-body metabolism and energetic balance. Throughout an unbiased mutagenesis approach in HD mice, we have found that Scn4a, a skeletal muscle–specific sodium channel gene, is a modifier of the disease. Mutations in Scn4a enhance HD disease progression and weight loss by accelerating muscle waste and cachexia, increasing skeletal muscle activity and energy demands. At the molecular level, Scn4a mutations activate AMP-activated protein kinase (AMPK), leading to a fibre switch towards more oxidative types. These adaptations seen in HD; Scn4a double mutant muscles are similar to those observed in healthy individuals after endurance exercise training regimes. This prompted us to assess the effects of an endurance exercise regime in HD mice, independently showing that skeletal muscle adaptations leading to the activation of AMPK are detrimental for HD pathogenesis. Although it is undeniable that physical exercise can lead to many health benefits, our work shows that, at least under certain situations such as in HD, an endurance exercise routine could be a detrimental therapeutic option.
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spelling pubmed-62106272018-11-05 Skeletal Muscle Modulates Huntington’s Disease Pathogenesis in Mice: Role of Physical Exercise Corrochano, Silvia Blanco, Gonzalo Acevedo-Arozena, Abraham J Exp Neurosci Commentary Huntington’s disease (HD) is a monogenic fatal neurodegenerative disorder. However, there is increasing evidence that HD is a pleiotropic systemic disorder. In particular, skeletal muscle metabolism is greatly affected in HD, which in turn can have a major impact on whole-body metabolism and energetic balance. Throughout an unbiased mutagenesis approach in HD mice, we have found that Scn4a, a skeletal muscle–specific sodium channel gene, is a modifier of the disease. Mutations in Scn4a enhance HD disease progression and weight loss by accelerating muscle waste and cachexia, increasing skeletal muscle activity and energy demands. At the molecular level, Scn4a mutations activate AMP-activated protein kinase (AMPK), leading to a fibre switch towards more oxidative types. These adaptations seen in HD; Scn4a double mutant muscles are similar to those observed in healthy individuals after endurance exercise training regimes. This prompted us to assess the effects of an endurance exercise regime in HD mice, independently showing that skeletal muscle adaptations leading to the activation of AMPK are detrimental for HD pathogenesis. Although it is undeniable that physical exercise can lead to many health benefits, our work shows that, at least under certain situations such as in HD, an endurance exercise routine could be a detrimental therapeutic option. SAGE Publications 2018-10-30 /pmc/articles/PMC6210627/ /pubmed/30397387 http://dx.doi.org/10.1177/1179069518809059 Text en © The Author(s) 2018 http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Commentary
Corrochano, Silvia
Blanco, Gonzalo
Acevedo-Arozena, Abraham
Skeletal Muscle Modulates Huntington’s Disease Pathogenesis in Mice: Role of Physical Exercise
title Skeletal Muscle Modulates Huntington’s Disease Pathogenesis in Mice: Role of Physical Exercise
title_full Skeletal Muscle Modulates Huntington’s Disease Pathogenesis in Mice: Role of Physical Exercise
title_fullStr Skeletal Muscle Modulates Huntington’s Disease Pathogenesis in Mice: Role of Physical Exercise
title_full_unstemmed Skeletal Muscle Modulates Huntington’s Disease Pathogenesis in Mice: Role of Physical Exercise
title_short Skeletal Muscle Modulates Huntington’s Disease Pathogenesis in Mice: Role of Physical Exercise
title_sort skeletal muscle modulates huntington’s disease pathogenesis in mice: role of physical exercise
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210627/
https://www.ncbi.nlm.nih.gov/pubmed/30397387
http://dx.doi.org/10.1177/1179069518809059
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