ArticleGlia2023
The role of FUT8-catalyzed core fucosylation in Alzheimer's amyloid-β oligomer-induced activation of human microglia.
Article in Glia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- Fut8-Mediated Core Fucosylation of Toll-Like Receptor 4 Exacerbates Periodontitis Via Hyperactivation of NF-κB Signalling.International dental journal · 2026Article
- Enzymatic glycosylation as a potential molecular link between Alzheimer's disease and glaucoma.International journal of ophthalmology · 2026Review
- L-fucose administration ameliorates chronic social defeat stress-induced depressive-like behaviors by restoring GDP-fucose biosynthetic activation and core fucosylation.Frontiers in immunology · 2026Article
- l-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer's synaptic deficits.Science advances · 2025Article
- FUT8 Regulates Cerebellar Neurogenesis and Development Through Maintaining the Level of Neural Cell Adhesion Molecule Cntn2.Molecular neurobiology · 2025Article
- Unique N-glycosylation signatures in human iPSC derived microglia activated by Aβ oligomer and lipopolysaccharide.Scientific reports · 2025Article
- Pathway enrichment in genome-wide analysis of longitudinal Alzheimer's disease biomarker endophenotypes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Novel human iPSC models of neuroinflammation in neurodegenerative disease and regenerative medicine.Trends in immunology · 2024Review
- Article
- The ketone body β-hydroxybutyrate shifts microglial metabolism and suppresses amyloid-β oligomer-induced inflammation in human microglia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Microglial contribution to the pathology of neurodevelopmental disorders in humans.Acta neuropathologica · 2023Review
- Human iPSC-derived glia models for the study of neuroinflammation.Journal of neuroinflammation · 2023Review
- Targeting protein glycosylation to regulate inflammation in the respiratory tract: novel diagnostic and therapeutic candidates for chronic respiratory diseases.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Fucosylation, especially core fucosylation of N-glycans catalyzed by α1-6 fucosyltransferase (fucosyltransferase 8 or FUT8), plays an important role in regulating the peripheral immune system and inflammation. However, its role in microglial activation is poorly understood. Here we used human induced pluripotent stem cells-derived microglia (hiMG) as a model to study the role of FUT8-catalyzed core fucosylation in amyloid-β oligomer (AβO)-induced microglial activation, in view of its significant relevance to the pathogenesis of Alzheimer's disease (AD). HiMG responded to AβO and lipopolysaccharides (LPS) with a pattern of pro-inflammatory activation as well as enhanced core fucosylation and FUT8 expression within 24 h. Furthermore, we found increased FUT8 expression in both human AD brains and microglia isolated from 5xFAD mice, a model of AD-like cerebral amyloidosis. Inhibition of fucosylation in AβO-stimulated hiMG reduced the induction of pro-inflammatory cytokines, suppressed the activation of p38MAPK, and rectified phagocytic deficits. Specific inhibition of FUT8 by siRNA-mediated knockdown also reduced AβO-induced pro-inflammatory cytokines. We further showed that p53 binds to the two consensus binding sites in the Fut8 promoter, and that p53 knockdown abolished FUT8 overexpression in AβO-activated hiMG. Taken together, our evidence supports that FUT8-catalyzed core fucosylation is a signaling pathway required for AβO-induced 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-inflammatory therapeutic target for AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.