{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:57:12Z","timestamp":1767769032807,"version":"3.48.0"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Alzheimer\u2019s disease (AD) is neurodegenerative disorder characterized by chronic inflammation in the brain. Chitinase-3-like 1 (CHI3L1), a secreted glycoprotein that is upregulated in a variety of diseases with chronic inflammation, represents a promising target for AD. Here, we studied the inhibitory effect of a novel CHI3L1 monoclonal antibody (H1) on memory impairment and neuroinflammation in Tg2576 transgenic mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      H1 was shown to cross the blood\u2013brain barrier selectively, as confirmed by fluorescence imaging. Tg2576 mice were administered H1 (2\u202fmg\/kg, i.v., weekly for 1 month), and cognitive functions were assessed through behavioral tests. H1 treatment alleviated memory impairment and reduced amyloid deposition and neuroinflammation both in Tg2576 mice and A\u03b2-induced BV-2 microglial cells. Mechanistically, H1 inhibited the ERK and NF-\u03baB signaling pathways and suppressed M1 microglial marker expression. Global proteomic analysis and gene expression profiling in BV-2 cells and Tg2576 mouse brains revealed a strong association between CHI3L1 and HAX1 expression. H1 therapy significantly reduced HAX1 levels in both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      models. Moreover, HAX1 induction by A\u03b2 or CHI3L1 was blocked by an NF-\u03baB inhibitor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that CHI3L1 monoclonal antibody therapy may attenuate cognitive decline in AD by modulating neuroinflamma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2025.1728279","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:52:13Z","timestamp":1767768733000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CHI3L1 monoclonal antibody therapy mitigates cognitive impairment by inhibiting neuroinflammation through ERK and NF-\u03baB pathway in Tg2576 mice"],"prefix":"10.3389","volume":"18","author":[{"given":"Hyeon Joo","family":"Ham","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Sik","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Sun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Hun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Ju","family":"Son","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Hun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Key-Hwan","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanseul","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaesuk","family":"Yun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Bae","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Ki","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Tae","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"471","DOI":"10.3390\/ijms21124471","article-title":"MAP\/ERK Signaling in developing cognitive and emotional function and its effect on pathological and neurodegenerative processes","volume":"21","author":"Albert-Gasco","year":"2020","journal-title":"Int. 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