Skeletal Muscle Is a Primary Target of SOD1G93A-Mediated Toxicity
Open accessAbstract
The antioxidant enzyme superoxide dismutase 1 (SOD1) is a critical player of the antioxidative defense whose activity is altered in several chronic diseases, including amyotrophic lateral sclerosis. However, how oxidative insult affects muscle homeostasis remains unclear. This study addresses the role of oxidative stress on muscle homeostasis and function by the generation of a transgenic mouse model expressing a mutant SOD1 gene (SOD1(G93A)) selectively in skeletal muscle. Transgenic mice developed progressive muscle atrophy, associated with a significant reduction in muscle strength, alterations in the contractile apparatus, and mitochondrial dysfunction. The analysis of molecular pathways associated with muscle atrophy revealed that accumulation of oxidative stress served as signaling molecules to initiate autophagy, one of the major intracellular degradation mechanisms. These data demonstrate that skeletal muscle is a primary target of SOD1(G93A) -mediated toxicity and disclose the molecular mechanism whereby oxidative stress triggers muscle atrophy.
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The effects of skeletal muscle-specific SOD1G93A expression are mitigated by siRNA-mediated MAP1LC3B knockdown and subsequent reduction of autophagy flux.
“but these effects are mitigated by siRNA-mediated MAP1LC3B knockdown and the subsequent reduction of autophagy flux [479].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [479]
In ALS, skeletal muscle-specific expression of SOD1G93A is associated with atrophy and elevated autophagy.
“In ALS, skeletal muscle-specific expression of SOD1G93A is associated with atrophy and elevated autophagy [479],”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [479]
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- Authors
- Dobrowolny, G., Aucello, M., Rizzuto, E., Beccafico, S., Mammucari, C., Bonconpagni, S., Belia, S., Wannenes, F., Nicoletti, C., Del Prete, Z., Rosenthal, N., Molinaro, M., Protasi, F., Fanò, G., Sandri, M., & Musarò, A.
- Affiliations
- Istituto Pasteur (IT)
- University of Chieti-Pescara (IT)
- University of Perugia (IT)
- European Molecular Biology Laboratory (IT)
- University of Padua (IT)
- Edith Cowan University (AU)
- Corresponding author
- Musarò, Antonio
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 8
- Issue
- 5
- Pages
- 425-436
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2084860871
- Cited by
- 513
- References
- 40
- Citations by year
- 2026: 19 · 2025: 17 · 2024: 28 · 2023: 29 · 2022: 21 · 2021: 38 · 2020: 25 · 2019: 35 · 2018: 38 · 2017: 17 · 2016: 27 · 2015: 30 · 2014: 32 · 2013: 40 · 2012: 34
- FWCI
- 11.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Compagnia di San Paolo
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- superoxide dismutase 1, SOD1 G93A mutation, amyotrophic lateral sclerosis, skeletal muscle, muscle atrophy, oxidative stress, autophagy, mitochondrial dysfunction, muscle strength, transgenic mouse model, muscle homeostasis
- MeSH terms
- Superoxide Dismutase-1, Animals, Autophagy, Mice, Transgenic, Motor Neurons, Muscle Contraction, Muscular Atrophy, Mutation, Nerve Degeneration, Sarcolemma, Spinal Cord, Superoxide Dismutase, Reactive Oxygen Species, Oxidative Stress, Muscle, Skeletal, Mice
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