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Title: Cytochrome P450 derived epoxidized fatty acids as a therapeutic tool against neuroinflammatory diseases.

Authors: Atone, Jogen; Wagner, Karen; Hashimoto, Kenji; Hammock, Bruce D

Published In Prostaglandins Other Lipid Mediat, (2020 Apr)

Abstract: Cytochrome P450 (CYP) metabolism of arachidonic acid (ARA) produces epoxy fatty acids (EpFAs) such as epoxyeicosatrienoic acids (EETs) that are known to exert protective effects in inflammatory disorders. Endogenous EpFAs are further metabolized into corresponding diols by the soluble epoxide hydrolase (sEH). Through inhibition of sEH, many studies have demonstrated the cardioprotective and renoprotective effects of EpFAs; however, the role of sEH inhibition in modulating the pathogenesis of neuroinflammatory disorders is less well described. In this review, we discuss the current knowledge surrounding the effects of sEH inhibition and EpFA action in neuroinflammatory disorders such as Parkinson's Disease (PD), stroke, depression, epilepsy, and Alzheimer's Disease (AD), as well as the potential mechanisms that underlie the therapeutic effects of sEH inhibition.

PubMed ID: 31698143 Exiting the NIEHS site

MeSH Terms: Animals; Central Nervous System Agents/pharmacology*; Central Nervous System Diseases/drug therapy*; Central Nervous System Diseases/metabolism; Cytochrome P-450 Enzyme System/metabolism*; Disease Models, Animal; Drug Evaluation, Preclinical; Epoxide Hydrolases/antagonists & inhibitors*; Epoxide Hydrolases/metabolism; Epoxy Compounds/metabolism*; Fatty Acids/metabolism*; Humans

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