{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:52:13Z","timestamp":1760151133037,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K09578, 18K15366"],"award-info":[{"award-number":["17K09578, 18K15366"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that shows progressive muscle weakness. A few treatments exist including symptomatic therapies, which can prolong survival or reduce a symptom; however, no fundamental therapies have been found. As a therapeutic strategy, enhancing muscle force is important for patients\u2019 quality of life. In this study, we focused on skeletal muscle-specific myosin regulatory light chain kinase (skMLCK), which potentially enhances muscle contraction, as overexpression of skMLCK was thought to improve muscle function. The adeno-associated virus serotype 6 encoding skMLCK (AAV6\/skMLCK) and eGFP (control) was produced and injected intramuscularly into the lower limbs of SOD1G37R mice, which are a familial ALS model. AAV6\/skMLCK showed the successful expression of skMLCK in the muscle tissues. Although the control did not affect the muscle force in both of the WT and SOD1G37R mice, AAV6\/skMLCK enhanced the twitch force of SOD1G37R mice and the tetanic force of WT and SOD1G37R mice. These results indicate that overexpression of skMLCK can enhance the tetanic force of healthy muscle as well as rescue weakened muscle function. In conclusion, the gene transfer of skMLCK has the potential to be a new therapy for ALS as well as for other neuromuscular diseases.<\/jats:p>","DOI":"10.3390\/ijms23031747","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T11:35:17Z","timestamp":1643974517000},"page":"1747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gene Transfer of Skeletal Muscle-Type Myosin Light Chain Kinase via Adeno-Associated Virus 6 Improves Muscle Functions in an Amyotrophic Lateral Sclerosis Mouse Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8991-0315","authenticated-orcid":false,"given":"Ryohei","family":"Oya","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Osaka University Graduate School of Medicine\/Frontier Biosciences, Osaka 565-0871, Japan"},{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Osaka University Graduate School of Medicine\/Frontier Biosciences, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuro","family":"Hitsumoto","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Osaka University Graduate School of Medicine\/Frontier Biosciences, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoya","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, The Jikei University School of Medicine, Tokyo 105-8461, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0671-793X","authenticated-orcid":false,"given":"Chisato","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Osaka University Graduate School of Medicine\/Frontier Biosciences, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Osaka University Graduate School of Medicine\/Frontier Biosciences, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-3680","authenticated-orcid":false,"given":"Hisakazu","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Osaka University Graduate School of Medicine\/Frontier Biosciences, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenori","family":"Inohara","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Takashima","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Osaka University Graduate School of Medicine\/Frontier Biosciences, Osaka 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/S0140-6736(17)31287-4","article-title":"Amyotrophic lateral sclerosis","volume":"390","author":"Hardiman","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nrn3430","article-title":"The changing scene of amyotrophic lateral sclerosis","volume":"14","author":"Robberecht","year":"2013","journal-title":"Nat. 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