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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doaj-ae44b67d063640b69db4ccffa5fb9d482021-07-23T13:49:36ZengMDPI AGJournal of Personalized Medicine2075-44262021-07-011167167110.3390/jpm11070671The Skeletal Muscle Emerges as a New Disease Target in Amyotrophic Lateral SclerosisOihane Pikatza-Menoio0Amaia Elicegui1Xabier Bengoetxea2Neia Naldaiz-Gastesi3Adolfo López de Munain4Gorka Gerenu5Francisco Javier Gil-Bea6Sonia Alonso-Martín7Neuromuscular Diseases Group, Neurosciences Area, Biodonostia Health Research Institute, 20014 Donostia/San Sebastián, SpainNeuromuscular Diseases Group, Neurosciences Area, Biodonostia Health Research Institute, 20014 Donostia/San Sebastián, SpainNeuromuscular Diseases Group, Neurosciences Area, Biodonostia Health Research Institute, 20014 Donostia/San Sebastián, SpainNeuromuscular Diseases Group, Neurosciences Area, Biodonostia Health Research Institute, 20014 Donostia/San Sebastián, SpainNeuromuscular Diseases Group, Neurosciences Area, Biodonostia Health Research Institute, 20014 Donostia/San Sebastián, SpainNeuromuscular Diseases Group, Neurosciences Area, Biodonostia Health Research Institute, 20014 Donostia/San Sebastián, SpainNeuromuscular Diseases Group, Neurosciences Area, Biodonostia Health Research Institute, 20014 Donostia/San Sebastián, SpainNeuromuscular Diseases Group, Neurosciences Area, Biodonostia Health Research Institute, 20014 Donostia/San Sebastián, SpainAmyotrophic 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.https://www.mdpi.com/2075-4426/11/7/671ALSskeletal muscleneuromuscular junctionmetabolismvesiclesdistal axonopathy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Oihane Pikatza-Menoio Amaia Elicegui Xabier Bengoetxea Neia Naldaiz-Gastesi Adolfo López de Munain Gorka Gerenu Francisco Javier Gil-Bea Sonia Alonso-Martín |
spellingShingle |
Oihane Pikatza-Menoio Amaia Elicegui Xabier Bengoetxea Neia Naldaiz-Gastesi Adolfo López de Munain Gorka Gerenu Francisco Javier Gil-Bea Sonia Alonso-Martín The Skeletal Muscle Emerges as a New Disease Target in Amyotrophic Lateral Sclerosis Journal of Personalized Medicine ALS skeletal muscle neuromuscular junction metabolism vesicles distal axonopathy |
author_facet |
Oihane Pikatza-Menoio Amaia Elicegui Xabier Bengoetxea Neia Naldaiz-Gastesi Adolfo López de Munain Gorka Gerenu Francisco Javier Gil-Bea Sonia Alonso-Martín |
author_sort |
Oihane Pikatza-Menoio |
title |
The Skeletal Muscle Emerges as a New Disease Target in Amyotrophic Lateral Sclerosis |
title_short |
The Skeletal Muscle Emerges as a New Disease Target in Amyotrophic Lateral Sclerosis |
title_full |
The Skeletal Muscle Emerges as a New Disease Target in Amyotrophic Lateral Sclerosis |
title_fullStr |
The Skeletal Muscle Emerges as a New Disease Target in Amyotrophic Lateral Sclerosis |
title_full_unstemmed |
The Skeletal Muscle Emerges as a New Disease Target in Amyotrophic Lateral Sclerosis |
title_sort |
skeletal muscle emerges as a new disease target in amyotrophic lateral sclerosis |
publisher |
MDPI AG |
series |
Journal of Personalized Medicine |
issn |
2075-4426 |
publishDate |
2021-07-01 |
description |
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. |
topic |
ALS skeletal muscle neuromuscular junction metabolism vesicles distal axonopathy |
url |
https://www.mdpi.com/2075-4426/11/7/671 |
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