Evidence map›Paper›PMID 36692036›Full record

ArticleGlia2023

The role of FUT8-catalyzed core fucosylation in Alzheimer's amyloid-β oligomer-induced activation of human microglia.

Lee-Way Jin, Jacopo di Lucente, Ulises Ruiz Mendiola, Xinyu Tang, Angela M Zivkovic, Carlito B Lebrilla, Izumi Maezawa

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Pathway enrichment in genome-wide analysis of longitudinal Alzheimer's disease biomarker endophenotypes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  9. Review
  10. Food & function · 2024
    Article
  11. 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 · 2023
    Article
  12. Review
  13. Review
  14. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Lee-Way JinDepartment of Pathology and Laboratory Medicine and M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, California, USA.
Jacopo di LucenteDepartment of Pathology and Laboratory Medicine and M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, California, USA.ORCID 0000-0001-5312-5542
Ulises Ruiz MendiolaDepartment of Pathology and Laboratory Medicine and M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, California, USA.
Xinyu TangDepartment of Nutrition, University of California, Davis, California, USA.
Angela M ZivkovicDepartment of Nutrition, University of California, Davis, California, USA.
Carlito B LebrillaDepartment of Chemistry, University of California, Davis, California, USA.
Izumi MaezawaDepartment of Pathology and Laboratory Medicine and M.I.N.D. Institute, University of California Davis Medical Center, Sacramento, California, USA.ORCID 0000-0002-8666-3520
University of California Davis Medical Center · USUniversity of California, Davis · US

Funding

UC Davis Alzheimer's Disease Research CenterP30AG072972 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Charles DeCarli, Rachel A Whitmer · 2021 to 2026
$25.2M
TRANSLOCATION OF p66Shc: KINETICS, FUNCTION, APOPTOSISP01AG025532 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KIM, KYOUNGMI · 2007 to 2017
$12.1M
Reversing the epigenetic code of aging through ketogenic dietsP01AG062817 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI RAMSEY, JON J. · 2019 to 2023
$11.4M
Comprehensive Characterization of Glycosylation Alterations in Alzheimer’s DiseaseR01AG062240 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI JIN, LEE-WAY, LEBRILLA, CARLITO B · 2018 to 2022
$3.3M
NIA NIH HHS P01 AG025532NIA NIH HHS P01 AG062817NIA NIH HHS P30 AG072972NIA NIH HHS R01 AG062240
6 · The paper itself

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.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsAmyloid beta-PeptidesAnimalsCatalysisCytokinesFucosyltransferasesHumansMiceMicrogliaTumor Suppressor Protein p53Amyloid beta-PeptidesCytokinesFucosyltransferasesTumor Suppressor Protein p53Alzheimer'samyloidfucosylationfucosyltransferaseglycosylationmicrogliap53

Identifiers

PMID36692036
PMCPMC11021125
OpenAlexW4317831028

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.