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Replenishing NAD(+) content reduces aspects of striated muscle disease in a dog model of Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in DMD gene and loss of the protein dystrophin, which ultimately leads to myofiber membrane fragility and necrosis, with eventual muscle atrophy and contractures. Affected boys typically die in their second or third decade...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694913/ https://www.ncbi.nlm.nih.gov/pubmed/38044436 http://dx.doi.org/10.1186/s13395-023-00328-w |
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author | Cardoso, Déborah Barthélémy, Inès Blot, Stéphane Muchir, Antoine |
author_facet | Cardoso, Déborah Barthélémy, Inès Blot, Stéphane Muchir, Antoine |
author_sort | Cardoso, Déborah |
collection | PubMed |
description | Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in DMD gene and loss of the protein dystrophin, which ultimately leads to myofiber membrane fragility and necrosis, with eventual muscle atrophy and contractures. Affected boys typically die in their second or third decade due to either respiratory failure or cardiomyopathy. Among the developed therapeutic strategies for DMD, gene therapy approaches partially restore micro-dystrophin or quasi-dystrophin expression. However, despite extensive attempts to develop definitive therapies for DMD, the standard of care remains corticosteroid, which has only palliative benefits. Animal models have played a key role in studies of DMD pathogenesis and treatment development. The golden retriever muscular dystrophy (GRMD) dog displays a phenotype aligning with the progressive course of DMD. Therefore, canine studies may translate better to humans. Recent studies suggested that nicotinamide adenine dinucleotide (NAD(+)) cellular content could be a critical determinant for striated muscle function. We showed here that NAD(+) content was decreased in the striated muscles of GRMD, leading to an alteration of one of NAD(+) co-substrate enzymes, PARP-1. Moreover, we showed that boosting NAD(+) content using nicotinamide (NAM), a natural NAD(+) precursor, modestly reduces aspects of striated muscle disease. Collectively, our results provide mechanistic insights into DMD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13395-023-00328-w. |
format | Online Article Text |
id | pubmed-10694913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106949132023-12-05 Replenishing NAD(+) content reduces aspects of striated muscle disease in a dog model of Duchenne muscular dystrophy Cardoso, Déborah Barthélémy, Inès Blot, Stéphane Muchir, Antoine Skelet Muscle Research Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in DMD gene and loss of the protein dystrophin, which ultimately leads to myofiber membrane fragility and necrosis, with eventual muscle atrophy and contractures. Affected boys typically die in their second or third decade due to either respiratory failure or cardiomyopathy. Among the developed therapeutic strategies for DMD, gene therapy approaches partially restore micro-dystrophin or quasi-dystrophin expression. However, despite extensive attempts to develop definitive therapies for DMD, the standard of care remains corticosteroid, which has only palliative benefits. Animal models have played a key role in studies of DMD pathogenesis and treatment development. The golden retriever muscular dystrophy (GRMD) dog displays a phenotype aligning with the progressive course of DMD. Therefore, canine studies may translate better to humans. Recent studies suggested that nicotinamide adenine dinucleotide (NAD(+)) cellular content could be a critical determinant for striated muscle function. We showed here that NAD(+) content was decreased in the striated muscles of GRMD, leading to an alteration of one of NAD(+) co-substrate enzymes, PARP-1. Moreover, we showed that boosting NAD(+) content using nicotinamide (NAM), a natural NAD(+) precursor, modestly reduces aspects of striated muscle disease. Collectively, our results provide mechanistic insights into DMD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13395-023-00328-w. BioMed Central 2023-12-04 /pmc/articles/PMC10694913/ /pubmed/38044436 http://dx.doi.org/10.1186/s13395-023-00328-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Cardoso, Déborah Barthélémy, Inès Blot, Stéphane Muchir, Antoine Replenishing NAD(+) content reduces aspects of striated muscle disease in a dog model of Duchenne muscular dystrophy |
title | Replenishing NAD(+) content reduces aspects of striated muscle disease in a dog model of Duchenne muscular dystrophy |
title_full | Replenishing NAD(+) content reduces aspects of striated muscle disease in a dog model of Duchenne muscular dystrophy |
title_fullStr | Replenishing NAD(+) content reduces aspects of striated muscle disease in a dog model of Duchenne muscular dystrophy |
title_full_unstemmed | Replenishing NAD(+) content reduces aspects of striated muscle disease in a dog model of Duchenne muscular dystrophy |
title_short | Replenishing NAD(+) content reduces aspects of striated muscle disease in a dog model of Duchenne muscular dystrophy |
title_sort | replenishing nad(+) content reduces aspects of striated muscle disease in a dog model of duchenne muscular dystrophy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694913/ https://www.ncbi.nlm.nih.gov/pubmed/38044436 http://dx.doi.org/10.1186/s13395-023-00328-w |
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