Evidence map›Paper›PMID 40264187›Full record

ArticleMolecular neurodegeneration2025

Inhibition of soluble epoxide hydrolase confers neuroprotection and restores microglial homeostasis in a tauopathy mouse model.

Shuo Wang, Chuangye Qi, Chetan Rajpurohit, Baijayanti Ghosh, Wen Xiong, Baiping Wang, Yanyan Qi, Sung Hee Hwang, Bruce D Hammock, Hongjie Li and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Shuo WangHuffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Chuangye QiHuffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Chetan RajpurohitHuffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Baijayanti GhoshHuffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Wen XiongHuffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Baiping WangHuffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Yanyan QiHuffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Sung Hee HwangDepartment of Entomology and Nematology and UC Davis Comprehensive Cancer Center, University of California, Davis, CA, USA.
Bruce D HammockDepartment of Entomology and Nematology and UC Davis Comprehensive Cancer Center, University of California, Davis, CA, USA.
Hongjie LiHuffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Li GanHelen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medicine, New York, NY, USA.
Hui ZhengHuffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. huiz@bcm.edu.ORCID http://orcid.org/0000-0002-5427-3798

Funding

Cure Alzheimer's Fund Not applicableHarrington Discovery Institute, University Hospitals A25-1690NIA NIH HHS 020670NIA NIH HHS 066606NIA NIH HHS 068031NINDS NIH HHS 093652
6 · The paper itself

Abstract

backgroundThe epoxyeicosatrienoic acids (EETs) are derivatives of the arachidonic acid metabolism with anti-inflammatory activities. However, their efficacy is limited due to the rapid hydrolysis by soluble epoxide hydrolase (sEH). Inhibition of sEH has been shown to stabilize the EETs and reduce neuroinflammation in Aβ mouse models of Alzheimer's disease (AD). However, the role of the sEH-EET signaling pathway in other CNS cell types and neurodegenerative conditions are less understood.

methodsHere we investigated the mechanisms and functional role of the sEH-EET axis in tauopathy by treating PS19 mice with a small molecule sEH inhibitor TPPU and by crossing the PS19 mice with Ephx2 (gene encoding sEH) knockout mice. This was followed by single-nucleus RNA-sequencing (snRNA-seq), biochemical and immunohistochemical analysis, and behavioral assessments. Additionally, we examined the effects of the sEH-EET pathway in primary microglia cultures and human induced pluripotent stem cell (iPSC)-derived neurons exhibiting seeding-induced Tau inclusions.

resultssEH inhibition improved cognitive function, rescued neuronal cell loss, and reduced Tau pathology and microglial reactivity. snRNA-seq revealed that TPPU treatment upregulated genes involved in actin cytoskeleton and excitatory synaptic pathways. Treatment of human iPSC-derived neurons with TPPU enhanced synaptic density without affecting Tau accumulation, suggesting a cell-autonomous neuroprotective effect of sEH blockade. Furthermore, sEH inhibition reversed disease-associated and interferon-responsive microglial states in PS19 mice, while EET supplementation promoted Tau phagocytosis and clearance in primary microglia cultures.

conclusionThese findings demonstrate that sEH blockade or EET augmentation confers therapeutic benefit in neurodegenerative tauopathies by simultaneously targeting neuronal and microglial pathways.

Indexed as

Epoxide HydrolasesMicrogliaNeuroprotectionTauopathiesAnimalsDisease Models, AnimalHomeostasisHumansMiceMice, KnockoutMice, TransgenicNeuroprotective AgentsEphx2 protein, mouseEpoxide HydrolasesNeuroprotective AgentsAlzheimer’s diseaseEpoxyeicosatrienoic acidsMicrogliaNeurodegenerationSoluble epoxide hydrolaseTau

Identifiers

PMID40264187
PMCPMC12016400

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.