{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:20:55Z","timestamp":1783120855569,"version":"3.54.6"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    As persistent elevation of transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) promotes fibrosis of muscles and joints and accelerates disease progression in amyotrophic lateral sclerosis (ALS), we investigated whether inhibition of TGF\u2010\u03b2 would be effective against both exacerbations. The effects of TGF\u2010\u03b2 and its inhibitor on myoblasts and fibroblasts were tested in\u00a0vitro and confirmed in\u00a0vivo, and the dual action of a TGF\u2010\u03b2 inhibitor in ameliorating the pathogenic role of TGF\u2010\u03b2 in ALS mice was identified. In the peripheral neuromuscular system, fibrosis in the muscles and joint cavities induced by excessive TGF\u2010\u03b2 causes joint contracture and muscular degeneration, which leads to motor dysfunction. In an ALS mouse model, an increase in TGF\u2010\u03b2 in the central nervous system (CNS), consistent with astrocyte activity, was associated with M1 microglial activity and pro\u2010inflammatory conditions, as well as with neuronal cell death. Treatment with the TGF\u2010\u03b2 inhibitor halofuginone could prevent musculoskeletal fibrosis, resulting in the alleviation of joint contracture and delay of motor deterioration in ALS mice. Halofuginone could also reduce glial cell\u2010induced neuroinflammation and neuronal apoptosis. These dual therapeutic effects on both the neuromuscular system and the CNS were observed from the beginning to the end stages of ALS; as a result, treatment with a TGF\u2010\u03b2 inhibitor from the early stage of disease delayed the time of symptom exacerbation in ALS mice, which led to prolonged survival.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16102-fig-0009-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16102","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T02:55:53Z","timestamp":1711076153000},"page":"2495-2514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dual effects of\n                    <scp>TGF<\/scp>\n                    \u2010\u03b2 inhibitor in\n                    <scp>ALS<\/scp>\n                    \u2010 inhibit contracture and neurodegeneration"],"prefix":"10.1111","volume":"168","author":[{"given":"Do\u2010Yeon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Neurology Seoul National University Hospital  Seoul South Korea"},{"name":"Department of Neurology Seoul National University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Nam","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University Hospital  Seoul South Korea"},{"name":"Department of Neurology Severance Hospital, Yonsei University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangkook","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Department Curamys Co., Ltd.  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology Seoul National University College of Medicine  Seoul South Korea"},{"name":"Department of Biomedical Sciences Seoul National University College of Medicine  Seoul South Korea"},{"name":"Neuroscience Research Institute, Seoul National University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7525-5313","authenticated-orcid":false,"given":"Jung\u2010Joon","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University Hospital  Seoul South Korea"},{"name":"Department of Neurology Seoul National University College of Medicine  Seoul South Korea"},{"name":"Neuroscience Research Institute, Seoul National University College of Medicine  Seoul South Korea"},{"name":"Wide River 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