ArticleMolecular neurobiology2018
Soluble Epoxide Hydrolase Inhibition Attenuates MPTP-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System: Involvement of α-Synuclein Aggregation and ER Stress.
Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- AA and Parkinson's Disease.Reviews of physiology, biochemistry and pharmacology · 2027Review
- The Roles of EETs in Neurological Disorders.CNS neuroscience & therapeutics · 2026Review
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Article
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 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
- Novel therapeutic targets to halt the progression of Parkinson's disease: an in-depth review on molecular signalling cascades.3 Biotech · 2023Review
- Aflatoxin BInternational journal of molecular sciences · 2023Article
- TPPU inhibits inflammation-induced excessive autophagy to restore the osteogenic differentiation potential of stem cells and improves alveolar ridge preservation.Scientific reports · 2023Article
- Cytochrome P450-derived eicosanoids in brain: From basic discovery to clinical translation.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Lipidome modulation by dietary omega-3 polyunsaturated fatty acid supplementation or selective soluble epoxide hydrolase inhibition suppresses rough LPS-accelerated glomerulonephritis in lupus-prone mice.Frontiers in immunology · 2023Article
- Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders.International journal of molecular sciences · 2022Review
- Kurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Inhibition of sEH via stabilizing the level of EETs alleviated Alzheimer's disease through GSK3β signaling pathway.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2021Article
- Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification.Scientific reports · 2021Observational
- Alterations of Cytochrome P450s and UDP-Glucuronosyltransferases in Brain Under Diseases and Their Clinical Significances.Frontiers in pharmacology · 2021Review
- Article
- Review
- Preparation and evaluation of soluble epoxide hydrolase inhibitors with improved physical properties and potencies for treating diabetic neuropathic pain.Bioorganic & medicinal chemistry · 2020Article
- A single meal has the potential to alter brain oxylipin content.Prostaglandins, leukotrienes, and essential fatty acids · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Soluble epoxide hydrolase (sEH) is widely expressed in the mammalian brain and possesses dual enzymatic activities, including C-terminal epoxide hydrolase (C-EH) which degrades epoxyeicosatrienoic acid (EET), a beneficial arachidonic acid metabolite. In the present study, the neuroprotective effect of sEH inhibition on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using genetic and pharmacological approaches. MPTP (15 mg/kg) was intraperitoneally injected in sEH knockout (KO) mice and C57BL/6J mice as wild-type (WT) mice. Compared with the MPTP-treated WT mice, MPTP-induced reductions in striatal dopamine content and nigral tyrosine hydroxylase level (TH, a biomarker of dopaminergic neurons) were less significant in the treated sEH mice. Furthermore, MPTP-induced HO-1 elevation (a redox-regulated protein), α-synuclein aggregation, and caspase 12 activation (a hallmark of ER stress) were less prominent in sEH KO mice than in WT mice. These data indicate that sEH KO mice are more resistant to MPTP-induced neurotoxicity. The pharmacological effect of N-[1-(1-oxopropyl)-4-piperidinyl]-N0-[4-(trifluoromethoxy)phenyl)-urea (TPPU, an sEH inhibitor) on MPTP-induced neurotoxicity was investigated in WT mice. TPPU (1 mg/kg, i.p.) attenuated MPTP-induced reduction in striatal dopamine content, TH-positive cell numbers, TH, and pro-caspase 9 protein levels (an initiator caspase of apoptosis) in mouse SN. Moreover, TPPU reduced MPTP-induced HO-1 elevation, α-synuclein aggregation and caspase 12 activation, indicating that TPPU is effective in attenuating MPTP-induced oxidative stress, apoptosis, protein aggregation, and ER stress. In conclusion, our study suggests that sEH is a potential target for developing therapies for parkinsonism. Furthermore, sEH inhibitors may be of clinical significance for treating CNS neurodegenerative diseases.
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