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In a previous study, it was reported that an increased level of CHI3L1 in plasma was found in AD patients. We investigated the inhibitory effect of 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-<jats:italic>N<\/jats:italic>-(4-ethylphenyl)butanamide (K284-6111), an inhibitor of chitinase 3 like 1 (CHI3L1), on memory impairment in A\u03b2<jats:sub>1\u201342<\/jats:sub>-infused mice, and microglial BV-2 cells and astrocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We examined whether K284-6111 (3\u00a0mg\/kg given orally for 4\u00a0weeks) prevents amyloidogenesis and memory loss in A\u03b2<jats:sub>1\u201342<\/jats:sub>-induced AD mice model. After intracerebroventrical (ICV) infusion of A\u03b2<jats:sub>1\u201342<\/jats:sub> for 14\u00a0days, the cognitive function was assessed by the Morris water maze test and passive avoidance test. K284-6111 treatment was found to reduce A\u03b2<jats:sub>1\u201342<\/jats:sub>-induced memory loss.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>A memory recovery effect was found to be associated with the reduction of A\u03b2<jats:sub>1\u201342<\/jats:sub>-induced expression of inflammatory proteins (iNOS, COX-2, GFAP, and Iba-1) and the suppression of CHI3L1 expression in the brain. Additionally, K284-6111 reduced A\u03b2<jats:sub>1\u201342<\/jats:sub>-induced \u03b2-secretase activity and A\u03b2 generation. Lipopolysaccharide (LPS)-induced (1\u00a0\u03bcg\/mL) expression of inflammatory (COX-2, iNOS, GFAP, Iba-1) and amyloidogenic proteins (APP, BACE1) were decreased in microglial BV-2 cells and cultured astrocytes by the K284-6111 treatment (0.5, 1, and 2\u00a0\u03bcM). Moreover, K284-6111 treatment suppressed p50 and p65 translocation into the nucleus, and phosphorylation of I\u03baB in vivo and in vitro.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>These results suggest that CHI3L1 inhibitor could be an applicable intervention drug in amyloidogenesis and neuroinflammation, thereby preventing memory dysfunction via inhibition of NF-\u03baB.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12974-018-1269-3","type":"journal-article","created":{"date-parts":[[2018,8,11]],"date-time":"2018-08-11T08:16:29Z","timestamp":1533975389000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["K284-6111 prevents the amyloid beta-induced neuroinflammation and impairment of recognition memory through inhibition of NF-\u03baB-mediated CHI3L1 expression"],"prefix":"10.1186","volume":"15","author":[{"given":"Ji Yeon","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Jun","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Cheon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Rack","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Kyung","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Bae","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Tae","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,8,11]]},"reference":[{"issue":"12","key":"1269_CR1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.jalz.2016.03.001","volume":"2016","author":"A Alzheimer's","year":"2016","unstructured":"Alzheimer's A. 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Please see the Retraction Notice for more detail:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s12974-025-03386-7","URL":"https:\/\/doi.org\/10.1186\/s12974-025-03386-7","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The experimental protocols were carried out according to the guidelines for animal experiments of the Institutional Animal Care and Use Committee (IACUC) of Laboratory Animal Research Center at Chungbuk National University, Korea (CBNUA-1073-17-01).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"224"}}