{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T03:05:26Z","timestamp":1783393526312,"version":"3.54.6"},"reference-count":34,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP23ek0109529,JP23ek0109548,24ek0109617,24ek0109735,24ek0109759,JP23fk0108672,JP23wm0325056"],"award-info":[{"award-number":["JP23ek0109529,JP23ek0109548,24ek0109617,24ek0109735,24ek0109759,JP23fk0108672,JP23wm0325056"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare of Japan","doi-asserted-by":"crossref","award":["JPMH22FC1013,24FC2002"],"award-info":[{"award-number":["JPMH22FC1013,24FC2002"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP22H02987,JP22K07507,JP22K15420,JP23K06954,JP24K10148,JP21K07427"],"award-info":[{"award-number":["JP22H02987,JP22K07507,JP22K15420,JP23K06954,JP24K10148,JP21K07427"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP22H04923"],"award-info":[{"award-number":["JP22H04923"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,9]]},"abstract":"<jats:p>\n                    Human T-lymphotropic virus type 1\u2013associated (HTLV-1\u2013associated) myelopathy (HAM, also known as tropical spastic paraparesis) is a rare neurodegenerative disease with largely elusive molecular mechanisms, impeding targeted therapeutic advancements. This study aimed to identify the critical molecule responsible for neuronal damage in HAM, its source, and the regulatory mechanisms controlling its expression. Utilizing patient-derived cells and established cell lines, we discovered that HTLV-1 Tax, in conjunction with specificity protein 1 (Sp1), enhanced the expression of repulsive guidance molecule A (RGMa), a protein known to contribute to neuronal damage. RGMa expression was specifically upregulated in HTLV-1\u2013infected cells from patients with HAM, particularly in those expressing HTLV-1 Tax. Furthermore, in CD4\n                    <jats:sup>+<\/jats:sup>\n                    cells from patients with HAM, the level of H3K27me3 methylation upstream of the\n                    <jats:italic>RGMA<\/jats:italic>\n                    gene locus was reduced, making\n                    <jats:italic>RGMA<\/jats:italic>\n                    more prone to constitutive expression. We demonstrated that HTLV-1\u2013infected cells in HAM inflict neuronal damage via RGMa. Crucially, the neutralizing antibody against RGMa, unasnemab (MT-3921), effectively mitigated this damage in a dose-responsive manner, highlighting RGMa\u2019s pivotal role in neuronal damage and its potential as a therapeutic target for alleviating neuronal damage in HAM.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.184530","type":"journal-article","created":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T14:00:26Z","timestamp":1749391226000},"source":"Crossref","is-referenced-by-count":5,"title":["Virus-induced RGMa expression drives neurodegeneration in HTLV-1\u2013associated myelopathy"],"prefix":"10.1172","volume":"10","author":[{"given":"Natsumi","family":"Araya","sequence":"first","affiliation":[{"name":"Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, 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