Evidence map›Paper›PMID 41162676›Full record

ArticleNature aging2025

Loss of MFE-2 impairs microglial lipid homeostasis and drives neuroinflammation in Alzheimer's pathogenesis.

Min Gao, Jing Bai, Fangzhou Lou, Yang Sun, Zhikai Wang, Xiaojie Cai, Yan Li, Fengjiao Zhang, Jihuan Liang, Xiangxiao Li and 5 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

  1. Review
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  3. Article
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  5. Article
  6. Review
  7. Food science & nutrition · 2026
    Article
  8. Review
  9. Article
  10. Article
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  13. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Min Gao *Precision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jing Bai *Precision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Fangzhou LouPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yang SunPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhikai WangPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaojie CaiPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0001-7297-4865
Yan LiPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Fengjiao ZhangPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jihuan LiangPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiangxiao LiPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yue WuPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ziyang ZhangPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Li FanPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xinping JinPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Honglin WangPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. honglin.wang@sjtu.edu.cn.ORCID http://orcid.org/0000-0001-6302-6927

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysregulated lipid metabolism promotes persistent microglial activation and neuroinflammation in Alzheimer's disease (AD), but the underlying pathogenic mechanisms remain to be elucidated, and druggable targets remain to be identified. Here we found that multifunctional enzyme type 2 (MFE-2), the key enzyme regulating fatty acid β-oxidation in the peroxisome, was downregulated in the microglia of humans with AD and AD model mice. Microglia-specific ablation of MFE-2 drove microglial abnormalities, neuroinflammation and Aβ deposition in AD models. Mechanistically, MFE-2 deficiency facilitated lipid accumulation, resulting in excessive arachidonic acid, mitochondrial reactive oxygen species and proinflammatory cytokine production by microglia. The compound 3-O-cyclohexane carbonyl-11-keto-β-boswellic acid (CKBA) bound to MFE-2 and restored MFE-2 levels, ameliorating AD pathology by inhibiting microglial overactivation. Collectively, our data revealed a pathogenic role of microglia with impaired lipid metabolism in AD and identified MFE-2 as a druggable target of CKBA, which restores its expression and has therapeutic potential for treating AD.

Indexed as

Alzheimer DiseaseHomeostasisLipid MetabolismMicrogliaNeuroinflammatory DiseasesAmyloid beta-PeptidesAnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutReactive Oxygen SpeciesAmyloid beta-PeptidesReactive Oxygen Species

Identifiers

PMID41162676

What OpenQuestion holds

Textmetadata
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.