{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T21:11:48Z","timestamp":1778361108360,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,19]],"date-time":"2024-05-19T00:00:00Z","timestamp":1716076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["MRC, 2017R1A5A2015541"],"award-info":[{"award-number":["MRC, 2017R1A5A2015541"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["2021RIS-001"],"award-info":[{"award-number":["2021RIS-001"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean government (MOE)","award":["MRC, 2017R1A5A2015541"],"award-info":[{"award-number":["MRC, 2017R1A5A2015541"]}]},{"name":"Korean government (MOE)","award":["2021RIS-001"],"award-info":[{"award-number":["2021RIS-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several clinical studies reported that the elevated expression of Chitinase-3-like 1 (CHI3L1) was observed in patients suffering from a wide range of diseases: cancer, metabolic, and neurological diseases. However, the role of CHI3L1 in AD is still unclear. Our previous study demonstrated that 2-({3-[2-(1-Cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}culfanyl)-N-(4-ethylphenyl)butanamide, a CHI3L1 inhibiting compound, alleviates memory and cognitive impairment and inhibits neuroinflammation in AD mouse models. In this study, we studied the detailed correlation of CHI3L1 and AD using serum from AD patients and using CHI3L1 knockout (KO) mice with A\u03b2 infusion (300 pmol\/day, 14 days). Serum levels of CHI3L1 were significantly elevated in patients with AD compared to normal subjects, and receiver operating characteristic (ROC) analysis data based on serum analysis suggested that CHI3L1 could be a significant diagnostic reference for AD. To reveal the role of CHI3L1 in AD, we investigated the CHI3L1 deficiency effect on memory impairment in A\u03b2-infused mice and microglial BV-2 cells. In CHI3L1 KO mice, A\u03b2 infusion resulted in lower levels of memory dysfunction and neuroinflammation compared to that of WT mice. CHI3L1 deficiency selectively inhibited phosphorylation of ERK and I\u03baB as well as inhibition of neuroinflammation-related factors in vivo and in vitro. On the other hand, treatment with recombinant CHI3L1 increased neuroinflammation-related factors and promoted phosphorylation of I\u03baB except for ERK in vitro. Web-based gene network analysis and our results showed that CHI3L1 is closely correlated with PTX3. Moreover, in AD patients, we found that serum levels of PTX3 were correlated with serum levels of CHI3L1 by Spearman correlation analysis. These results suggest that CHI3L1 deficiency could inhibit AD development by blocking the ERK-dependent PTX3 pathway.<\/jats:p>","DOI":"10.3390\/ijms25105550","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T08:20:31Z","timestamp":1716193231000},"page":"5550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inhibition of Amyloid-\u03b2 (A\u03b2)-Induced Cognitive Impairment and Neuroinflammation in CHI3L1 Knockout Mice through Downregulation of ERK-PTX3 Pathway"],"prefix":"10.3390","volume":"25","author":[{"given":"Hyeon Joo","family":"Ham","sequence":"first","affiliation":[{"name":"College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Sun","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ja Keun","family":"Koo","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaesuk","family":"Yun","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7520-6909","authenticated-orcid":false,"given":"Dong Ju","family":"Son","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6656-6523","authenticated-orcid":false,"given":"Sang-Bae","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-9575","authenticated-orcid":false,"given":"Jin Tae","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.3233\/JAD-180183","article-title":"The Effects of Music Therapy on Cognition, Psychiatric Symptoms, and Activities of Daily Living in Patients with Alzheimer\u2019s Disease","volume":"64","author":"Lyu","year":"2018","journal-title":"J. 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