ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2020
Pharmacological Inhibition of Soluble Epoxide Hydrolase as a New Therapy for Alzheimer's Disease.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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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.
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Who cites it
57 citing papers in PubMed, 84 citations in OpenAlex.
- PTUPB improves cognitive function in Alzheimer's disease associated with enhancing cerebral vascular myogenic response and attenuating vascular remodeling.GeroScience · 2026Article
- Topliss-Guided Optimization of Acetanilide-Based Soluble Epoxide Hydrolase Inhibitors: Exploring the Pentafluorosulfanyl Group as a Potency-Enhancing Motif.ChemMedChem · 2026Article
- Review
- 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
- Activation of anti-inflammatory pathways by polyunsaturated fatty acid signaling may protect neurodevelopment in children prenatally exposed to methylmercury.Environmental health : a global access science source · 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
- 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
- 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
- Article
- Microglial pro-inflammatory mechanisms induced by monomeric C-reactive protein are counteracted by soluble epoxide hydrolase inhibitors.International immunopharmacology · 2025Article
- Inhibition of soluble epoxide hydrolase confers neuroprotection and restores microglial homeostasis in a tauopathy mouse model.Molecular neurodegeneration · 2025Article
- Soluble Epoxide Hydrolase Inhibition Improves Alzheimer's Disease Hallmarks: Correlation with Peripheral Inflammation and Gut Microbiota Modulation.Aging and disease · 2025Article
- Novel Soluble Epoxide Hydrolase Inhibitor: Toward Regulatory Preclinical Studies.ACS pharmacology & translational science · 2025Article
- Effects of molecular interactions between the exposome and oxylipin metabolism on healthspan.Frontiers in physiology · 2025Review
- Inhibiting the soluble epoxide hydrolase increases the EpFAs and ERK1/2 expression in the hippocampus of LiCl-pilocarpine post-status epilepticus rat model.IBRO neuroscience reports · 2024Article
- Inhibition of Soluble Epoxide Hydrolase Ameliorates Cerebral Blood Flow Autoregulation and Cognition in Alzheimer's Disease and Diabetes-Related Dementia Rat Models.bioRxiv : the preprint server for biology · 2024Article
- Novel molecular mechanism driving neuroprotection after soluble epoxide hydrolase inhibition: Insights for Alzheimer's disease therapeutics.CNS neuroscience & therapeutics · 2024Article
- The role of CYP-sEH derived lipid mediators in regulating mitochondrial biology and cellular senescence: implications for the aging heart.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
The inhibition of the enzyme soluble epoxide hydrolase (sEH) has demonstrated clinical therapeutic effects in several peripheral inflammatory-related diseases, with 3 compounds in clinical trials. However, the role of this enzyme in the neuroinflammation process has been largely neglected. Herein, we disclose the pharmacological validation of sEH as a novel target for the treatment of Alzheimer's disease (AD). Evaluation of cognitive impairment and pathological hallmarks were used in 2 models of age-related cognitive decline and AD using 3 structurally different and potent sEH inhibitors as chemical probes. sEH is upregulated in brains from AD patients. Our findings supported the beneficial effects of central sEH inhibition, regarding reducing cognitive impairment, neuroinflammation, tau hyperphosphorylation pathology, and the number of amyloid plaques. This study suggests that inhibition of inflammation in the brain by targeting sEH is a relevant therapeutic strategy 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.