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However, its role in microglial activation is poorly understood. Here we used human induced pluripotent stem cells\u2010derived microglia (hiMG) as a model to study the role of FUT8\u2010catalyzed core fucosylation in amyloid\u2010\u03b2 oligomer (A\u03b2O)\u2010induced microglial activation, in view of its significant relevance to the pathogenesis of Alzheimer's disease (AD). HiMG responded to A\u03b2O and lipopolysaccharides (LPS) with a pattern of pro\u2010inflammatory activation as well as enhanced core fucosylation and FUT8 expression within 24\u2009h. Furthermore, we found increased FUT8 expression in both human AD brains and microglia isolated from 5xFAD mice, a model of AD\u2010like cerebral amyloidosis. Inhibition of fucosylation in A\u03b2O\u2010stimulated hiMG reduced the induction of pro\u2010inflammatory cytokines, suppressed the activation of p38MAPK, and rectified phagocytic deficits. Specific inhibition of FUT8 by siRNA\u2010mediated knockdown also reduced A\u03b2O\u2010induced pro\u2010inflammatory cytokines. We further showed that p53 binds to the two consensus binding sites in the <jats:italic>Fut8<\/jats:italic> promoter, and that p53 knockdown abolished FUT8 overexpression in A\u03b2O\u2010activated hiMG. Taken together, our evidence supports that FUT8\u2010catalyzed core fucosylation is a signaling pathway required for A\u03b2O\u2010induced microglia activation and that FUT8 is a component of the p53 signaling cascade regulating microglial behavior. Because microglia are a key driver of AD pathogenesis, our results suggest that microglial FUT8 could be an anti\u2010inflammatory therapeutic target for AD.<\/jats:p>","DOI":"10.1002\/glia.24345","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T11:16:21Z","timestamp":1674558981000},"page":"1346-1359","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The role of <scp>FUT8<\/scp>\u2010catalyzed core fucosylation in Alzheimer's amyloid\u2010\u03b2 oligomer\u2010induced activation of human microglia"],"prefix":"10.1002","volume":"71","author":[{"given":"Lee\u2010Way","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and M.I.N.D. 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