The Skeletal Muscle Emerges as a New Disease Target in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons (MNs) and severe muscle atrophy without effective treatment. Most research on ALS has been focused on the study of MNs and supporting cells of the central nervous system....

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Bibliographic Details
Published in:Journal of personalized medicine 2021-07, Vol.11 (7), p.671
Main Authors: Pikatza-Menoio, Oihane, Elicegui, Amaia, Bengoetxea, Xabier, Naldaiz-Gastesi, Neia, López de Munain, Adolfo, Gerenu, Gorka, Gil-Bea, Francisco Javier, Alonso-Martín, Sonia
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
Atrophy
Autophagy
Central nervous system
Disease
Genotype & phenotype
Homeostasis
Metabolism
Mortality
Motor neurons
Musculoskeletal system
Mutation
Myogenesis
Neurodegeneration
Neurodegenerative diseases
Neuromuscular diseases
Neurons
Pathology
Patients
Physiology
Precision medicine
Regeneration
Review
Skeletal muscle
Spinal cord
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Summary:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons (MNs) and severe muscle atrophy without effective treatment. Most research on ALS has been focused on the study of MNs and supporting cells of the central nervous system. Strikingly, the recent observations of pathological changes in muscle occurring before disease onset and independent from MN degeneration have bolstered the interest for the study of muscle tissue as a potential target for delivery of therapies for ALS. Skeletal muscle has just been described as a tissue with an important secretory function that is toxic to MNs in the context of ALS. Moreover, a fine-tuning balance between biosynthetic and atrophic pathways is necessary to induce myogenesis for muscle tissue repair. Compromising this response due to primary metabolic abnormalities in the muscle could trigger defective muscle regeneration and neuromuscular junction restoration, with deleterious consequences for MNs and thereby hastening the development of ALS. However, it remains puzzling how backward signaling from the muscle could impinge on MN death. This review provides a comprehensive analysis on the current state-of-the-art of the role of the skeletal muscle in ALS, highlighting its contribution to the neurodegeneration in ALS through backward-signaling processes as a newly uncovered mechanism for a peripheral etiopathogenesis of the disease.
ISSN:2075-4426
2075-4426
DOI:10.3390/jpm11070671