ArticleProceedings of the National Academy of Sciences of the United States of America2018
Soluble epoxide hydrolase plays a key role in the pathogenesis of Parkinson's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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87 citing papers in PubMed, 130 citations in OpenAlex.
- The Roles of EETs in Neurological Disorders.CNS neuroscience & therapeutics · 2026Review
- The Emerging Parkinson's Disease Oxylipin-Ome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Iron chelation targets lipid metabolism to reduce white matter injury in germinal matrix hemorrhage.Cell death & disease · 2026Article
- Sources of Oxidative Stress in Parkinson's Disease: Pathways and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Review
- Hepatic sEH drives stress-induced neuroinflammation via IL-6 and liver-brain axis.Frontiers in immunology · 2026Article
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- 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
- Inhibition of Soluble Epoxide Hydrolase Prevents Docetaxel-Induced Painful Peripheral Neuropathy.International journal of molecular sciences · 2025Article
- Article
- Inhibition of soluble epoxide hydrolase confers neuroprotection and restores microglial homeostasis in a tauopathy mouse model.Molecular neurodegeneration · 2025Article
- The prognostic significance of epoxide hydrolases in colorectal cancer.Biochemistry and biophysics reports · 2025Article
- Effects of molecular interactions between the exposome and oxylipin metabolism on healthspan.Frontiers in physiology · 2025Review
- 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
- Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies.Metabolites · 2024Review
- Doxycycline-Loaded Calcium Phosphate Nanoparticles with a Pectin Coat Can Ameliorate Lipopolysaccharide-Induced Neuroinflammation Via Enhancing AMPK.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis.Clinical immunology (Orlando, Fla.) · 2023Article
- Cytochrome P450 and Epoxide Hydrolase Metabolites in Aβ and tau-induced Neurodegeneration: Insights frombioRxiv : the preprint server for biology · 2023Article
- [European journal of nuclear medicine and molecular imaging · 2023Article
- Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase attenuated particulate matter 2.5 exposure mediated lung injury.Journal of hazardous materials · 2023Article
- Mangiferin and Taurine Ameliorate MSRV Infection by Suppressing NF-κB Signaling.Microbiology spectrum · 2023Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Parkinson's disease (PD) is characterized as a chronic and progressive neurodegenerative disorder, and the deposition of specific protein aggregates of α-synuclein, termed Lewy bodies, is evident in multiple brain regions of PD patients. Although there are several available medications to treat PD symptoms, these medications do not prevent the progression of the disease. Soluble epoxide hydrolase (sEH) plays a key role in inflammation associated with the pathogenesis of PD. Here we found that MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced neurotoxicity in the mouse striatum was attenuated by subsequent repeated administration of TPPU, a potent sEH inhibitor. Furthermore, deletion of the sEH gene protected against MPTP-induced neurotoxicity, while overexpression of sEH in the striatum significantly enhanced MPTP-induced neurotoxicity. Moreover, the expression of the sEH protein in the striatum from MPTP-treated mice or postmortem brain samples from patients with dementia of Lewy bodies (DLB) was significantly higher compared with control groups. Interestingly, there was a positive correlation between sEH expression and phosphorylation of α-synuclein in the striatum. Oxylipin analysis showed decreased levels of 8,9-epoxy-5Z,11Z,14Z-eicosatrienoic acid in the striatum of MPTP-treated mice, suggesting increased activity of sEH in this region. Interestingly, the expression of sEH mRNA in human PARK2 iPSC-derived neurons was higher than that of healthy control. Treatment with TPPU protected against apoptosis in human PARK2 iPSC-derived dopaminergic neurons. These findings suggest that increased activity of sEH in the striatum plays a key role in the pathogenesis of neurodegenerative disorders such as PD and DLB. Therefore, sEH may represent a promising therapeutic target for α-synuclein-related neurodegenerative disorders.
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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.