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Published on: August 15, 2017
Soluble epoxide hydrolase: Mechanisms and therapeutic potential in psychiatric and neurological disorders
Ming-Ming Zhao1, Jian-Jun Yang2, Kenji Hashimoto3
1Chiba University Center for Forensic Mental Health, Chiba, Japan; Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China; Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou University, Zhengzhou, P.R. China.
Abstract:
Soluble epoxide hydrolase (sEH), encoded by the EPHX2 gene, is a critical enzyme involved in the metabolism of polyunsaturated fatty acids, specifically anti-inflammatory epoxy fatty acids (EpFAs). By converting EpFAs into less active forms, sEH promotes inflammation. Preclinical data using knock-out and overexpression of the Ephx2 gene have demonstrated its key role in the development and progression of symptoms in various disease models. Inhibition of sEH increases EpFAs, thereby enhancing their anti-inflammatory effects and reducing the levels of pro-inflammatory mediators. Numerous preclinical studies suggest that sEH inhibitors show promise in reducing inflammation and its related symptoms across various diseases, highlighting their therapeutic potential. This chapter reviews the role of sEH in the development and progression of various disorders including psychiatric disorders (depression, schizophrenia, autism spectrum disorder), neurological disorders (Alzheimer's disease, Parkinson's disease, brain injury), and pain.
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