Center of Excellence for Aging and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, United States.
Department of Entomology & UCD Comprehensive Cancer Center, NIEHS-UCD Superfund Research Program, University of California - Davis, United States.
Prog Neurobiol. 2019 Jan;172:23-39. doi: 10.1016/j.pneurobio.2018.11.001. Epub 2018 Nov 14.
Soluble epoxide hydrolase (sEH) degrades epoxides of fatty acids including epoxyeicosatrienoic acid isomers (EETs), which are produced as metabolites of the cytochrome P450 branch of the arachidonic acid pathway. EETs exert a variety of largely beneficial effects in the context of inflammation and vascular regulation. sEH inhibition is shown to be therapeutic in several cardiovascular and renal disorders, as well as in peripheral analgesia, via the increased availability of anti-inflammatory EETs. The success of sEH inhibitors in peripheral systems suggests their potential in targeting inflammation in the central nervous system (CNS) disorders. Here, we describe the current roles of sEH in the pathology and treatment of CNS disorders such as stroke, traumatic brain injury, Parkinson's disease, epilepsy, cognitive impairment, dementia and depression. In view of the robust anti-inflammatory effects of stem cells, we also outlined the potency of stem cell treatment and sEH inhibitors as a combination therapy for these CNS disorders. This review highlights the gaps in current knowledge about the pathologic and therapeutic roles of sEH in CNS disorders, which should guide future basic science research towards translational and clinical applications of sEH inhibitors for treatment of neurological diseases.
可溶性环氧化物水解酶 (sEH) 可降解脂肪酸的环氧化物，包括环氧二十碳三烯酸异构体 (EETs)，它们是花生四烯酸途径细胞色素 P450 分支的代谢产物。EETs 在炎症和血管调节方面发挥了多种有益作用。sEH 抑制已被证明在几种心血管和肾脏疾病以及外周镇痛中具有治疗作用，这是通过增加抗炎 EETs 的可用性实现的。sEH 抑制剂在外周系统中的成功表明它们有可能针对中枢神经系统 (CNS) 疾病中的炎症。在这里，我们描述了 sEH 在中风、创伤性脑损伤、帕金森病、癫痫、认知障碍、痴呆和抑郁症等 CNS 疾病的病理和治疗中的当前作用。鉴于干细胞具有强大的抗炎作用，我们还概述了干细胞治疗和 sEH 抑制剂作为这些 CNS 疾病联合治疗的潜力。这篇综述强调了当前关于 sEH 在 CNS 疾病中的病理和治疗作用的知识空白，这应该指导未来的基础科学研究，以将 sEH 抑制剂的转化和临床应用用于治疗神经疾病。
