{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T10:50:50Z","timestamp":1789815050433,"version":"4.0.1"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,27]],"date-time":"2025-04-27T00:00:00Z","timestamp":1745712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP17K07087"],"award-info":[{"award-number":["JP17K07087"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP23K06313"],"award-info":[{"award-number":["JP23K06313"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP20K07220"],"award-info":[{"award-number":["JP20K07220"]}]},{"name":"Asahikawa Medical Center, the National Hospital Organization","award":["JP17K07087"],"award-info":[{"award-number":["JP17K07087"]}]},{"name":"Asahikawa Medical Center, the National Hospital Organization","award":["JP23K06313"],"award-info":[{"award-number":["JP23K06313"]}]},{"name":"Asahikawa Medical Center, the National Hospital Organization","award":["JP20K07220"],"award-info":[{"award-number":["JP20K07220"]}]},{"name":"The Ichiro Kanehara Foundation","award":["JP17K07087"],"award-info":[{"award-number":["JP17K07087"]}]},{"name":"The Ichiro Kanehara Foundation","award":["JP23K06313"],"award-info":[{"award-number":["JP23K06313"]}]},{"name":"The Ichiro Kanehara Foundation","award":["JP20K07220"],"award-info":[{"award-number":["JP20K07220"]}]},{"name":"Takahashi-Zaidan","award":["JP17K07087"],"award-info":[{"award-number":["JP17K07087"]}]},{"name":"Takahashi-Zaidan","award":["JP23K06313"],"award-info":[{"award-number":["JP23K06313"]}]},{"name":"Takahashi-Zaidan","award":["JP20K07220"],"award-info":[{"award-number":["JP20K07220"]}]},{"name":"Asahikawa Medical University","award":["JP17K07087"],"award-info":[{"award-number":["JP17K07087"]}]},{"name":"Asahikawa Medical University","award":["JP23K06313"],"award-info":[{"award-number":["JP23K06313"]}]},{"name":"Asahikawa Medical University","award":["JP20K07220"],"award-info":[{"award-number":["JP20K07220"]}]},{"name":"Akita University Graduate School of Medicine","award":["JP17K07087"],"award-info":[{"award-number":["JP17K07087"]}]},{"name":"Akita University Graduate School of Medicine","award":["JP23K06313"],"award-info":[{"award-number":["JP23K06313"]}]},{"name":"Akita University Graduate School of Medicine","award":["JP20K07220"],"award-info":[{"award-number":["JP20K07220"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chitinase-3-like protein 1 (CHI3L1) has been implicated in multiple sclerosis (MS) pathology, yet its precise role remains unclear. To elucidate its involvement, we performed proteomic analysis of cerebrospinal fluid (CSF) from relapsing-remitting MS (RRMS) patients using two-dimensional difference gel electrophoresis (2D-DIGE). CHI3L1 emerged as the most upregulated protein in recurrent RRMS. ELISA confirmed significantly elevated CHI3L1 levels in recurrent RRMS and secondary progressive MS (SPMS) patients, with levels decreasing in steroid responders but increasing in non-responders. Immunohistochemistry of MS brain autopsies revealed CHI3L1 expression predominantly in mature oligodendrocytes. In an experimental autoimmune encephalomyelitis (EAE) model, CHI3L1 was highly expressed in the spinal cord, particularly in oligodendrocytes and microglia\/macrophages. Functional studies demonstrated that recombinant CHI3L1 (rCHI3L1) protected oligodendrocytes from LPC-induced cell death by attenuating ER stress (GRP78, ORP150). Moreover, rCHI3L1 counteracted IFN-\u03b2- and PSL-mediated inhibition of oligodendrocyte differentiation. In microglia, rCHI3L1 suppressed LPS-induced proinflammatory markers (IL-1\u03b2, iNOS). In vivo, rCHI3L1 administration significantly mitigated EAE severity by reducing gliosis, demyelination, and axonal degeneration. These findings highlight CHI3L1 as a critical modulator of neuroinflammation and oligodendrocyte survival, positioning it as a promising therapeutic target for MS.<\/jats:p>","DOI":"10.3390\/ijms26094160","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T11:48:33Z","timestamp":1745840913000},"page":"4160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Implications of Chitinase 3-like 1 Protein in the Pathogenesis of Multiple Sclerosis in Autopsied Brains and a Murine Model"],"prefix":"10.3390","volume":"26","author":[{"given":"Yoshio","family":"Bando","sequence":"first","affiliation":[{"name":"Department of Anatomy, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Akita, Japan"},{"name":"Department of Functional Anatomy and Neuroscience, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa 078-8510, Hokkaido, Japan"},{"name":"Department of Clinical Research, National Hospital Organization, Asahikawa Medical Center, 7 Hanasakichiyo, Asahikawa 070-8644, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, National Hospital Organization, Asahikawa Medical Center, 7 Hanasakichiyo, Asahikawa 070-8644, Hokkaido, Japan"},{"name":"Department of Neurology, National Hospital Organization, Asahikawa Medical Center, 7 Hanasakichiyo, Asahikawa 070-8644, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, National Hospital Organization, Asahikawa Medical Center, 7 Hanasakichiyo, Asahikawa 070-8644, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Hospital Organization, Asahikawa Medical Center, 7 Hanasakichiyo, Asahikawa 070-8644, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Yahara","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Hospital Organization, Asahikawa Medical Center, 7 Hanasakichiyo, Asahikawa 070-8644, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e200370","DOI":"10.1212\/NXI.0000000000200370","article-title":"Contribution of Blood Biomarkers to Multiple Sclerosis Diagnosis","volume":"2","author":"Comabella","year":"2025","journal-title":"Neurol. 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