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Galectin\u20103 (Gal\u20103) is closely related to microglial activation in the nervous system and can promote the aggregation of cancer cells in tumors. This study aimed to investigate the mechanism by which farnesylthiosalicylic acid (FTS) affects neuroinflammation in A\u03b2<jats:sub>1\u201342<\/jats:sub> mice through Gal\u20103.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used the Morris water maze, reverse transcription\u2013polymerase chain reaction (RT\u2013PCR), Western blotting, enzyme\u2010linked immunosorbent assay (ELISA), and immunofluorescence to conduct our study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FTS reduced the levels of proinflammatory factors and microglial activation in A\u03b2<jats:sub>1\u201342<\/jats:sub> mice. FTS inhibited total and membrane expression levels of Gal\u20103 in A\u03b2<jats:sub>1\u201342<\/jats:sub> mice, and the anti\u2010inflammatory effect of FTS was reversed by Gal\u20103\u2013adeno\u2010associated viral (AAV). FTS reduced the expression levels of toll\u2010like receptors (TLRs), effects that were reversed by Gal\u20103\u2010AAV. Moreover, FTS ameliorated A\u03b2 oligomerization and accumulation in A\u03b2<jats:sub>1\u201342<\/jats:sub> mice, effects that were also reversed by Gal\u20103\u2010AAV. FTS, through the inhibition of the Gal\u20103\u2013c\u2010Jun N\u2010terminal kinase (JNK) pathway, reduced PS1 expression; in addition, inhibition of Gal\u20103 increased the A\u03b2\u2010degrading enzymes in A\u03b2<jats:sub>1\u201342<\/jats:sub> mice. FTS\u2010induced improvements in cognition in A\u03b2<jats:sub>1\u201342<\/jats:sub> mice were reversed by Gal\u20103\u2010AAV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>FTS may through inhibiting Gal\u20103 reduce the expression of TLR4 and CD14 and alleviate A\u03b2 pathology, downregulating A\u03b2\u2010stimulated TLR2, TLR4, and CD14 expression, and thus alleviate neuroinflammation in A\u03b2<jats:sub>1\u201342<\/jats:sub> mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70127","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T04:39:13Z","timestamp":1732682353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Farnesylthiosalicylic Acid Through Inhibition of Galectin\u20103 Improves Neuroinflammation in Alzheimer Disease via Multiple 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