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Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1(G93A) Mice Predates Disease Onset and Is A Promising Therapeutic Target
Patients with ALS show, in addition to the loss of motor neurons in the spinal cord, brainstem, and cerebral cortex, an abnormal depletion of energy stores alongside hypermetabolism. In this study, we show that bioenergetic defects and muscle remodeling occur in skeletal muscle of the SOD1(G93A) mou...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200935/ https://www.ncbi.nlm.nih.gov/pubmed/32371370 http://dx.doi.org/10.1016/j.isci.2020.101087 |
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author | Scaricamazza, Silvia Salvatori, Illari Giacovazzo, Giacomo Loeffler, Jean Philippe Renè, Frederique Rosina, Marco Quessada, Cyril Proietti, Daisy Heil, Constantin Rossi, Simona Battistini, Stefania Giannini, Fabio Volpi, Nila Steyn, Frederik J. Ngo, Shyuan T. Ferraro, Elisabetta Madaro, Luca Coccurello, Roberto Valle, Cristiana Ferri, Alberto |
author_facet | Scaricamazza, Silvia Salvatori, Illari Giacovazzo, Giacomo Loeffler, Jean Philippe Renè, Frederique Rosina, Marco Quessada, Cyril Proietti, Daisy Heil, Constantin Rossi, Simona Battistini, Stefania Giannini, Fabio Volpi, Nila Steyn, Frederik J. Ngo, Shyuan T. Ferraro, Elisabetta Madaro, Luca Coccurello, Roberto Valle, Cristiana Ferri, Alberto |
author_sort | Scaricamazza, Silvia |
collection | PubMed |
description | Patients with ALS show, in addition to the loss of motor neurons in the spinal cord, brainstem, and cerebral cortex, an abnormal depletion of energy stores alongside hypermetabolism. In this study, we show that bioenergetic defects and muscle remodeling occur in skeletal muscle of the SOD1(G93A) mouse model of ALS mice prior to disease onset and before the activation of muscle denervation markers, respectively. These changes in muscle physiology were followed by an increase in energy expenditure unrelated to physical activity. Finally, chronic treatment of SOD1(G93A) mice with Ranolazine, an FDA-approved inhibitor of fatty acid β-oxidation, led to a decrease in energy expenditure in symptomatic SOD1(G93A) mice, and this occurred in parallel with a robust, albeit temporary, recovery of the pathological phenotype. |
format | Online Article Text |
id | pubmed-7200935 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-72009352020-05-07 Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1(G93A) Mice Predates Disease Onset and Is A Promising Therapeutic Target Scaricamazza, Silvia Salvatori, Illari Giacovazzo, Giacomo Loeffler, Jean Philippe Renè, Frederique Rosina, Marco Quessada, Cyril Proietti, Daisy Heil, Constantin Rossi, Simona Battistini, Stefania Giannini, Fabio Volpi, Nila Steyn, Frederik J. Ngo, Shyuan T. Ferraro, Elisabetta Madaro, Luca Coccurello, Roberto Valle, Cristiana Ferri, Alberto iScience Article Patients with ALS show, in addition to the loss of motor neurons in the spinal cord, brainstem, and cerebral cortex, an abnormal depletion of energy stores alongside hypermetabolism. In this study, we show that bioenergetic defects and muscle remodeling occur in skeletal muscle of the SOD1(G93A) mouse model of ALS mice prior to disease onset and before the activation of muscle denervation markers, respectively. These changes in muscle physiology were followed by an increase in energy expenditure unrelated to physical activity. Finally, chronic treatment of SOD1(G93A) mice with Ranolazine, an FDA-approved inhibitor of fatty acid β-oxidation, led to a decrease in energy expenditure in symptomatic SOD1(G93A) mice, and this occurred in parallel with a robust, albeit temporary, recovery of the pathological phenotype. Elsevier 2020-04-21 /pmc/articles/PMC7200935/ /pubmed/32371370 http://dx.doi.org/10.1016/j.isci.2020.101087 Text en © 2020 The Author(s) 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 | Article Scaricamazza, Silvia Salvatori, Illari Giacovazzo, Giacomo Loeffler, Jean Philippe Renè, Frederique Rosina, Marco Quessada, Cyril Proietti, Daisy Heil, Constantin Rossi, Simona Battistini, Stefania Giannini, Fabio Volpi, Nila Steyn, Frederik J. Ngo, Shyuan T. Ferraro, Elisabetta Madaro, Luca Coccurello, Roberto Valle, Cristiana Ferri, Alberto Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1(G93A) Mice Predates Disease Onset and Is A Promising Therapeutic Target |
title | Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1(G93A) Mice Predates Disease Onset and Is A Promising Therapeutic Target |
title_full | Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1(G93A) Mice Predates Disease Onset and Is A Promising Therapeutic Target |
title_fullStr | Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1(G93A) Mice Predates Disease Onset and Is A Promising Therapeutic Target |
title_full_unstemmed | Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1(G93A) Mice Predates Disease Onset and Is A Promising Therapeutic Target |
title_short | Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1(G93A) Mice Predates Disease Onset and Is A Promising Therapeutic Target |
title_sort | skeletal-muscle metabolic reprogramming in als-sod1(g93a) mice predates disease onset and is a promising therapeutic target |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200935/ https://www.ncbi.nlm.nih.gov/pubmed/32371370 http://dx.doi.org/10.1016/j.isci.2020.101087 |
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