ArticleScience translational medicine2020
An epoxide hydrolase inhibitor reduces neuroinflammation in a mouse model of Alzheimer's disease.
Article in Science translational medicine, 2020. 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 88 papers.
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.
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.
Who cites it
88 citing papers in PubMed, 131 citations in OpenAlex.
- PTUPB improves cognitive function in Alzheimer's disease associated with enhancing cerebral vascular myogenic response and attenuating vascular remodeling.GeroScience · 2026Article
- Alzheimer's disease target and drug discovery by leveraging multiomics and electronic health data.Nature neuroscience · 2026Article
- Review
- Inhibition of Soluble Epoxide Hydrolase Rescues Cognitive Deficits by Preserving Neurovascular Integrity and Attenuating Glial- and Neuropathology in Diabetic-Related Dementia.bioRxiv : the preprint server for biology · 2026Article
- Iron chelation targets lipid metabolism to reduce white matter injury in germinal matrix hemorrhage.Cell death & disease · 2026Article
- Allosteric ensembles elucidate mechanisms of inhibition in the human soluble epoxide hydrolase.Communications biology · 2026Article
- Epoxide Hydrolase Family: Biological Functions, Disease Mechanisms, and Emerging Therapeutic Strategies.Biology · 2026Review
- The aging gut-glia-immune axis in alzheimer's disease: microbiome-derived mediators of neuroinflammation and therapeutic innovation.GeroScience · 2026Review
- Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026Review
- Liquid Chromatography-Tandem Mass Spectrometry-Based Targeted Lipidomic Analysis of Obesity-Related Colorectal Cancer: Potential Roles of the CYP Eicosanoid Pathway.The Journal of nutrition · 2026Article
- Nanomaterial strategies for mitigating protein misfolding and neuroinflammation in neurodegenerative diseases.Zoological research · 2026Review
- Epoxy-oxylipins direct monocyte fate in inflammatory resolution in humans.Nature communications · 2026Article
- Metabolic alteration in oxylipins and endocannabinoids point to an important role for soluble epoxide hydrolase and inflammation in Alzheimer's disease-finding from Alzheimer's Disease Neuroimaging Initiative.Alzheimer's research & therapy · 2026Article
- Hepatic sEH drives stress-induced neuroinflammation via IL-6 and liver-brain axis.Frontiers in immunology · 2026Article
- Mapping key mitochondrial genes in Alzheimer's disease through human tissue and iPSC derived neurons.Scientific reports · 2025Article
- A Neural-Glial Model of the ApoE-SORT1-FABP7 Axis Tied to Sleep Disruption and Alzheimer's Disease Pathophysiology.Biomolecules · 2025Review
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Air pollution and Alzheimer disease phenotype deplete esterified proresolving lipid mediator reserves in the brain.JCI insight · 2025Article
- Exploration of biomarkers of Alzheimer's disease based on orthogonal multi-task canonical correlation analysis.BMC medical imaging · 2025Article
- The soluble epoxide hydrolase inhibitor TPPU alleviates Aβ-mediated neuroinflammatory responses in Drosophila melanogaster and cellular models of alzheimer's disease.Journal of inflammation (London, England) · 2025Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Neuroinflammation has been increasingly recognized to play a critical role in Alzheimer's disease (AD). The epoxy fatty acids (EpFAs) are derivatives of the arachidonic acid metabolism pathway and have anti-inflammatory activities. However, their efficacy is limited because of their rapid hydrolysis by the soluble epoxide hydrolase (sEH). We report that sEH is predominantly expressed in astrocytes and is elevated in postmortem brain tissue from patients with AD and in the 5xFAD β amyloid mouse model of AD. The amount of sEH expressed in AD mouse brains correlated with a reduction in brain EpFA concentrations. Using a specific small-molecule sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), we report that TPPU treatment protected wild-type mice against LPS-induced inflammation in vivo. Long-term administration of TPPU to the 5xFAD mouse model via drinking water reversed microglia and astrocyte reactivity and immune pathway dysregulation. This was associated with reduced β amyloid pathology and improved synaptic integrity and cognitive function on two behavioral tests. TPPU treatment correlated with an increase in EpFA concentrations in the brains of 5xFAD mice, demonstrating brain penetration and target engagement of this small molecule. These findings support further investigation of TPPU as a potential therapeutic agent for the treatment of AD.
Indexed as
Identifiers
What OpenQuestion holds
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.