Occludin regulation of blood-brain barrier and potential therapeutic target in ischemic stroke.
Occludin regulation of blood-brain barrier and potential therapeutic target in ischemic stroke.
复制标题
DOI：
10.4103/bc.bc_29_20
复制
发表时间：
2020-07
影响因子：
1.9
通讯作者：
Qi Z
中科院分区：
文献类型：
--
作者：
Yuan S;Liu KJ;Qi Z
封闭蛋白是血脑屏障的重要组成部分，近年来成为血脑屏障损伤研究的热点。许多研究表明闭合蛋白可以调节血脑屏障的完整性和通透性。血脑屏障的功能依赖于脑内皮细胞中occludin蛋白的表达水平。此外，occludin可能作为急性缺血性卒中后出血转化的潜在生物标志物。本文就occludin在血脑屏障完整性中的作用及其对缺血性脑卒中后血脑屏障通透性的调节机制作一综述。已经发现多种因素调节闭合蛋白在维持BBB通透性中的功能，例如基质金属蛋白酶介导的切割、磷酸化、泛素化和相关的炎症因子。此外，多种信号通路参与调节闭合蛋白的表达，包括核因子-κ B、促分裂原活化蛋白激酶、蛋白激酶c、RhoK和ERK 1/2。介绍了以闭合蛋白为靶点的缺血性卒中治疗干预措施，包括常压高氧、中药、化学药物、基因、类固醇激素、小分子肽和其他疗法。由于occludin已被证明在调节血脑屏障的完整性中发挥关键作用，进一步的临床前研究将有助于评估和验证occludin作为缺血性卒中的可行治疗靶点。
Occludin is a key structural component of the blood–brain barrier (BBB) that has recently become an important focus of research in BBB damages. Many studies have demonstrated that occludin could regulate the integrity and permeability of the BBB. The function of BBB depends on the level of occludin protein expression in brain endothelial cells. Moreover, occludin may serve as a potential biomarker for hemorrhage transformation after acute ischemic stroke. In this review, we summarize the role of occludin in BBB integrity and the regulatory mechanisms of occludin in the permeability of BBB after ischemic stroke. Multiple factors have been found to regulate occludin protein functions in maintaining BBB permeability, such as Matrix metalloproteinas-mediated cleavage, phosphorylation, ubiquitination, and related inflammatory factors. In addition, various signaling pathways participate in regulating the occludin expression, including nuclear factor-kappa B, mitogen-activated protein kinase, protein kinase c, RhoK, and ERK1/2. Emerging therapeutic interventions for ischemic stroke targeting occludin are described, including normobaric hyperoxia, Chinese medicine, chemical drugs, genes, steroid hormones, small molecular peptides, and other therapies. Since occludin has been shown to play a critical role in regulating BBB integrity, further preclinical studies will help evaluate and validate occludin as a viable therapeutic target for ischemic stroke.
登录
查看更多内容
影响因子：
3.4
作者：
Capaldo, Christopher T.;Nusrat, Asma
通讯作者：
Nusrat, Asma
影响因子：
11
作者：
Chen, Yi-Shen;Chen, Kuan-Hung;Lin, Chung-Ren
通讯作者：
Lin, Chung-Ren
影响因子：
6.6
作者：
Bellmann, Christian;Schreivogel, Sophie;Blasig, Ingolf E.
通讯作者：
Blasig, Ingolf E.
DOI：
10.1152/ajpheart.00554.2005
发表时间：
2006-02-01
影响因子：
4.8
作者：
DeMaio, L;Rouhanizadeh, M;Hsiai, TK
通讯作者：
Hsiai, TK
影响因子：
4.8
作者：
Antonetti, DA;Barber, AJ;Gardner, TW
通讯作者：
Gardner, TW