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The Interplay of Mitophagy and Inflammation in Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease caused by a pathogenic disruption of the DYSTROPHIN gene that results in non-functional dystrophin protein. DMD patients experience loss of ambulation, cardiac arrhythmia, metabolic syndrome, and respiratory failure. At the molec...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307817/ https://www.ncbi.nlm.nih.gov/pubmed/34357020 http://dx.doi.org/10.3390/life11070648 |
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author | Reid, Andrea L. Alexander, Matthew S. |
author_facet | Reid, Andrea L. Alexander, Matthew S. |
author_sort | Reid, Andrea L. |
collection | PubMed |
description | Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease caused by a pathogenic disruption of the DYSTROPHIN gene that results in non-functional dystrophin protein. DMD patients experience loss of ambulation, cardiac arrhythmia, metabolic syndrome, and respiratory failure. At the molecular level, the lack of dystrophin in the muscle results in myofiber death, fibrotic infiltration, and mitochondrial dysfunction. There is no cure for DMD, although dystrophin-replacement gene therapies and exon-skipping approaches are being pursued in clinical trials. Mitochondrial dysfunction is one of the first cellular changes seen in DMD myofibers, occurring prior to muscle disease onset and progresses with disease severity. This is seen by reduced mitochondrial function, abnormal mitochondrial morphology and impaired mitophagy (degradation of damaged mitochondria). Dysfunctional mitochondria release high levels of reactive oxygen species (ROS), which can activate pro-inflammatory pathways such as IL-1β and IL-6. Impaired mitophagy in DMD results in increased inflammation and further aggravates disease pathology, evidenced by increased muscle damage and increased fibrosis. This review will focus on the critical interplay between mitophagy and inflammation in Duchenne muscular dystrophy as a pathological mechanism, as well as describe both candidate and established therapeutic targets that regulate these pathways. |
format | Online Article Text |
id | pubmed-8307817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83078172021-07-25 The Interplay of Mitophagy and Inflammation in Duchenne Muscular Dystrophy Reid, Andrea L. Alexander, Matthew S. Life (Basel) Review Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease caused by a pathogenic disruption of the DYSTROPHIN gene that results in non-functional dystrophin protein. DMD patients experience loss of ambulation, cardiac arrhythmia, metabolic syndrome, and respiratory failure. At the molecular level, the lack of dystrophin in the muscle results in myofiber death, fibrotic infiltration, and mitochondrial dysfunction. There is no cure for DMD, although dystrophin-replacement gene therapies and exon-skipping approaches are being pursued in clinical trials. Mitochondrial dysfunction is one of the first cellular changes seen in DMD myofibers, occurring prior to muscle disease onset and progresses with disease severity. This is seen by reduced mitochondrial function, abnormal mitochondrial morphology and impaired mitophagy (degradation of damaged mitochondria). Dysfunctional mitochondria release high levels of reactive oxygen species (ROS), which can activate pro-inflammatory pathways such as IL-1β and IL-6. Impaired mitophagy in DMD results in increased inflammation and further aggravates disease pathology, evidenced by increased muscle damage and increased fibrosis. This review will focus on the critical interplay between mitophagy and inflammation in Duchenne muscular dystrophy as a pathological mechanism, as well as describe both candidate and established therapeutic targets that regulate these pathways. MDPI 2021-07-04 /pmc/articles/PMC8307817/ /pubmed/34357020 http://dx.doi.org/10.3390/life11070648 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Reid, Andrea L. Alexander, Matthew S. The Interplay of Mitophagy and Inflammation in Duchenne Muscular Dystrophy |
title | The Interplay of Mitophagy and Inflammation in Duchenne Muscular Dystrophy |
title_full | The Interplay of Mitophagy and Inflammation in Duchenne Muscular Dystrophy |
title_fullStr | The Interplay of Mitophagy and Inflammation in Duchenne Muscular Dystrophy |
title_full_unstemmed | The Interplay of Mitophagy and Inflammation in Duchenne Muscular Dystrophy |
title_short | The Interplay of Mitophagy and Inflammation in Duchenne Muscular Dystrophy |
title_sort | interplay of mitophagy and inflammation in duchenne muscular dystrophy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307817/ https://www.ncbi.nlm.nih.gov/pubmed/34357020 http://dx.doi.org/10.3390/life11070648 |
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