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Year : 2022  |  Volume : 65  |  Issue : 1  |  Page : 1-11

Epoxyeicosatrienoic acids and soluble epoxide hydrolase in physiology and diseases of the central nervous system

1 Department of Anesthesiology, Taipei Veterans General Hospital; Department of Anesthesiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
2 Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan

Correspondence Address:
Dr. Yi-Hsuan Lee
Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cjp.cjp_80_21

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Epoxyeicosatrienoic acids (EETs) are fatty acid signaling molecules synthesized by cytochrome P450 epoxygenases from arachidonic acid. The biological activity of EETs is terminated when being metabolized by soluble epoxide hydrolase (sEH), a process that serves as a key regulator of tissue EETs levels. EETs act through several signaling pathways to mediate various beneficial effects, including anti-inflammation, anti-apoptosis, and anti-oxidation with relieve of endoplasmic reticulum stress, thereby sEH has become a potential therapeutic target in cardiovascular disease and cancer therapy. Enzymes for EET biosynthesis and metabolism are both widely detected in both neuron and glial cells in the central nervous system (CNS). Recent studies discovered that astrocyte-derived EETs not only mediate neurovascular coupling and neuronal excitability by maintaining glutamate homeostasis but also glia-dependent neuroprotection. Genetic ablation as well as pharmacologic inhibition of sEH has greatly helped to elucidate the physiologic actions of EETs, and maintaining or elevating brain EETs level has been demonstrated beneficial effects in CNS disease models. Here, we review the literature regarding the studies on the bioactivity of EETs and their metabolic enzyme sEH with special attention paid to their action mechanisms in the CNS, including their modulation of neuronal activity, attenuation of neuroinflammation, regulation of cerebral blood flow, and improvement of neuronal and glial cells survival. We further reviewed the recent advance on the potential application of sEH inhibition for treating cerebrovascular disease, epilepsy, and pain disorder.

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