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

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.

• Authors: Jogen Atone, Karen Wagner, Kenji Hashimoto, Bruce D Hammock
• Journal: Prostaglandins & other lipid mediators (Prostaglandins Other Lipid Mediat) Vol. 147 Pg. 106385 (04 2020) ISSN: 1098-8823 [Print] United States
• PMID: 31698143 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Central Nervous System Agents
• Epoxy Compounds
• Fatty Acids
• Cytochrome P-450 Enzyme System
• Epoxide Hydrolases

Topics

• Animals
• Central Nervous System Agents (pharmacology)
• Central Nervous System Diseases (drug therapy, metabolism)
• Cytochrome P-450 Enzyme System (metabolism)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Epoxide Hydrolases (antagonists & inhibitors, metabolism)
• Epoxy Compounds (metabolism)
• Fatty Acids (metabolism)
• Humans