Inhibition of soluble epoxide hydrolase as a therapeutic approach for blood-brain barrier dysfunction

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie Pub Date : 2024-03-24 DOI:10.1016/j.biochi.2024.03.015

Shuo Li, Huijia Song, Yanping Sun, Yongjun Sun, Huimin Zhang, Zibin Gao

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Abstract

The blood-brain barrier (BBB) is a protective semi-permeable structure that regulates the exchange of biomolecules between the peripheral blood and the central nervous system (CNS). Due to its specialized tight junctions and low vesicle trafficking, the BBB strictly limits the paracellular passage and transcellular transport of molecules to maintain the physiological condition of brain tissues. BBB breakdown is associated with many CNS disorders. Soluble epoxide hydrolase (sEH) is a hydrolase enzyme that converts epoxy-fatty acids (EpFAs) to their corresponding diols and is involved in the onset and progression of multiple diseases. EpFAs play a protective role in the central nervous system via preventing neuroinflammation, making sEH a potential therapeutic target for CNS diseases. Recent studies showed that sEH inhibition prevented BBB impairment caused by stroke, hemorrhage, traumatic brain injury, hyperglycemia and sepsis via regulating the expression of tight junctions. In this review, the protective actions of sEH inhibition on BBB and potential mechanisms are summarized, and some important questions that remain to be resolved are also addressed.

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将抑制可溶性环氧化物水解酶作为治疗血脑屏障功能障碍的一种方法。

血脑屏障（BBB）是一种半渗透性保护结构，负责调节外周血和中枢神经系统（CNS）之间的生物大分子交换。由于血脑屏障具有专门的紧密连接和较低的囊泡贩运，因此它严格限制分子的细胞旁通过和跨细胞转运，以维持脑组织的生理状态。BBB 的破坏与许多中枢神经系统疾病有关。可溶性环氧化物水解酶（sEH）是一种水解酶，能将环氧脂肪酸（EpFAs）转化为相应的二醇，与多种疾病的发生和发展有关。环氧脂肪酸通过防止神经炎症在中枢神经系统中发挥保护作用，使 sEH 成为中枢神经系统疾病的潜在治疗靶点。最近的研究表明，抑制 sEH 可通过调节紧密连接的表达，防止中风、出血、脑外伤、高血糖和败血症引起的 BBB 损伤。本综述总结了抑制 sEH 对 BBB 的保护作用及其潜在机制，并探讨了一些有待解决的重要问题。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimie 生物-生化与分子生物学

CiteScore

7.20

自引率

2.60%

发文量

219

审稿时长

40 days

期刊介绍： Biochimie publishes original research articles, short communications, review articles, graphical reviews, mini-reviews, and hypotheses in the broad areas of biology, including biochemistry, enzymology, molecular and cell biology, metabolic regulation, genetics, immunology, microbiology, structural biology, genomics, proteomics, and molecular mechanisms of disease. Biochimie publishes exclusively in English. Articles are subject to peer review, and must satisfy the requirements of originality, high scientific integrity and general interest to a broad range of readers. Submissions that are judged to be of sound scientific and technical quality but do not fully satisfy the requirements for publication in Biochimie may benefit from a transfer service to a more suitable journal within the same subject area.