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In the brain, CHI3L1 is primarily provided by astrocytes and heralds the reactive, neurotoxic state triggered by inflammation and other stress signals. However, how CHI3L1 acts in neuroinflammation or how it contributes to AD and relevant neurodegenerative conditions remains unknown. In peripheral tissues, our group and others have uncovered that CHI3L1 is a master regulator for a wide range of injury and repair events, including the innate immunity pathway that resembles the neuroinflammation process governed by microglia and astrocytes. Based on assessment of current knowledge regarding CHI3L1 biology, we hypothesize that CHI3L1 functions as a signaling molecule mediating distinct neuroinflammatory responses in brain cells and misfunctions to precipitate neurodegeneration. We also recommend future research directions to validate such assertions for better understanding of disease mechanisms.<\/jats:p>","DOI":"10.1002\/alz.12612","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T07:02:11Z","timestamp":1646204531000},"page":"9-24","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":149,"title":["Potential role of chitinase\u20103\u2010like protein 1 (CHI3L1\/YKL\u201040) in neurodegeneration and Alzheimer's disease"],"prefix":"10.1002","volume":"19","author":[{"given":"Kevin","family":"Connolly","sequence":"first","affiliation":[{"name":"Department of Molecular Biology Cell Biology, and Biochemistry Brown University  Providence Rhode Island USA"},{"name":"Graduate Program in Molecular Biology Cell Biology, and Biochemistry, Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Lehoux","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Cell Biology, and Biochemistry Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"O'Rourke","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Cell Biology, and Biochemistry Brown University  Providence Rhode Island USA"},{"name":"Graduate Program in Pathobiology Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Assetta","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Cell Biology, and Biochemistry Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guzide Ayse","family":"Erdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Cell Biology, and Biochemistry Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack A","family":"Elias","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Cell Biology, and Biochemistry Brown University  Providence Rhode Island USA"},{"name":"Department of Molecular Microbiology and Immunology Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Geun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-8008","authenticated-orcid":false,"given":"Yu\u2010Wen Alvin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Cell Biology, and Biochemistry Brown University  Providence Rhode Island USA"},{"name":"Department of Neurology Warren Alpert Medical School of Brown University  Providence Rhode Island USA"},{"name":"Center for Translational Neuroscience Robert J. and Nancy D. 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