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Despite intense research efforts and numerous clinical trials, it is still an incurable disease. ALS had long been considered a pure motor neuron disease; however, recent studies have shown that motor neuron protection is not sufficient to prevent the course of the disease since the dismantlement of neuromuscular junctions occurs before motor neuron degeneration. Skeletal muscle alterations have been described in the early stages of the disease, and they seem to be mainly involved in the \u201cdying back\u201d phenomenon of motor neurons and metabolic dysfunctions. In recent years, skeletal muscles have been considered crucial not only for the etiology of ALS but also for its treatment. Here, we review clinical and preclinical studies that targeted skeletal muscles and discuss the different approaches, including pharmacological interventions, supplements or diets, genetic modifications, and training programs.<\/jats:p>","DOI":"10.3390\/cells10030525","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T10:36:37Z","timestamp":1614681397000},"page":"525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Skeletal Muscle in ALS: An Unappreciated Therapeutic Opportunity?"],"prefix":"10.3390","volume":"10","author":[{"given":"Silvia","family":"Scaricamazza","sequence":"first","affiliation":[{"name":"Fondazione Santa Lucia IRCCS, c\/o CERC, 00143 Rome, Italy"},{"name":"Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Illari","family":"Salvatori","sequence":"additional","affiliation":[{"name":"Fondazione Santa Lucia IRCCS, c\/o CERC, 00143 Rome, Italy"},{"name":"Department of Experimental Medicine, University of Rome \u201cLa Sapienza\u201d, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ferri","sequence":"additional","affiliation":[{"name":"Fondazione Santa Lucia IRCCS, c\/o CERC, 00143 Rome, Italy"},{"name":"Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Valle","sequence":"additional","affiliation":[{"name":"Fondazione Santa Lucia IRCCS, c\/o CERC, 00143 Rome, Italy"},{"name":"Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hardiman, O., Al-chalabi, A., Chio, A., Corr, E.M., Robberecht, W., Shaw, P.J., and Simmons, Z. 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