{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T11:36:49Z","timestamp":1774352209726,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T00:00:00Z","timestamp":1632528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["AL170061(W81XWH1810684)"],"award-info":[{"award-number":["AL170061(W81XWH1810684)"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["R01NS105621"],"award-info":[{"award-number":["R01NS105621"]}]},{"name":"NIH","award":["R01 HL138570"],"award-info":[{"award-number":["R01 HL138570"]}]},{"name":"NIH","award":["R01AG056919"],"award-info":[{"award-number":["R01AG056919"]}]},{"name":"NIH","award":["R01AR061385"],"award-info":[{"award-number":["R01AR061385"]}]},{"name":"NIH","award":["R01AR070752"],"award-info":[{"award-number":["R01AR070752"]}]},{"name":"NIH","award":["R01DK106394"],"award-info":[{"award-number":["R01DK106394"]}]},{"DOI":"10.13039\/100000971","name":"ALS Association","doi-asserted-by":"publisher","award":["16-IIP-288"],"award-info":[{"award-number":["16-IIP-288"]}],"id":[{"id":"10.13039\/100000971","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bank of America Victor E. Peas Foundation","award":["#####"],"award-info":[{"award-number":["#####"]}]},{"name":"Kansas City Consortium on Musculoskeletaal Diseases","award":["#####"],"award-info":[{"award-number":["#####"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Respiratory failure from progressive respiratory muscle weakness is the most common cause of death in amyotrophic lateral sclerosis (ALS). Defects in neuromuscular junctions (NMJs) and progressive NMJ loss occur at early stages, thus stabilizing and preserving NMJs represents a potential therapeutic strategy to slow ALS disease progression. Here we demonstrate that NMJ damage is repaired by MG53, an intrinsic muscle protein involved in plasma membrane repair. Compromised diaphragm muscle membrane repair and NMJ integrity are early pathological events in ALS. Diaphragm muscles from ALS mouse models show increased susceptibility to injury and intracellular MG53 aggregation, which is also a hallmark of human muscle samples from ALS patients. We show that systemic administration of recombinant human MG53 protein in ALS mice protects against injury to diaphragm muscle, preserves NMJ integrity, and slows ALS disease progression. As MG53 is present in circulation in rodents and humans under physiological conditions, our findings provide proof-of-concept data supporting MG53 as a potentially safe and effective therapy to mitigate ALS progression.<\/jats:p>","DOI":"10.3390\/antiox10101522","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T01:59:47Z","timestamp":1632707987000},"page":"1522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["MG53 Preserves Neuromuscular Junction Integrity and Alleviates ALS Disease Progression"],"prefix":"10.3390","volume":"10","author":[{"given":"Jianxun","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Kinesiology, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USA"},{"name":"Department of Physiology, Kansas City University of Medicine and Biosciences, Kansas City, MO 64106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8784-4702","authenticated-orcid":false,"given":"Ang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USA"},{"name":"Department of Physiology, Kansas City University of Medicine and Biosciences, Kansas City, MO 64106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USA"},{"name":"Department of Physiology, Kansas City University of Medicine and Biosciences, Kansas City, MO 64106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kansas City University of Medicine and Biosciences, Kansas City, MO 64106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-4654","authenticated-orcid":false,"given":"Dosuk","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kansas City University of Medicine and Biosciences, Kansas City, MO 64106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyle W.","family":"Ostrow","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingsong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USA"},{"name":"Department of Physiology, Kansas City University of Medicine and Biosciences, Kansas City, MO 64106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/s00335-011-9339-1","article-title":"SOD1 and TDP-43 animal models of amyotrophic lateral sclerosis: Recent advances in understanding disease toward the development of clinical treatments","volume":"22","author":"Joyce","year":"2011","journal-title":"Mamm. 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