Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders.
Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders.
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DOI：
10.1016/j.brainres.2015.07.005
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发表时间：
2015-12-02
期刊：
影响因子：
2.9
通讯作者：
Trotti D
中科院分区：
文献类型：
--
作者：
Qosa H;Miller DS;Pasinelli P;Trotti D
血脑屏障 (BBB) 为中枢神经系统提供保护，使其免受循环化学物质的影响，其强度是通过内皮细胞之间的紧密连接以及调节中枢神经系统和血液之间交换的多种转运蛋白来维持的。限制大量毒素和治疗剂渗透性的最重要的转运蛋白是 ABC 转运蛋白。其中研究最多的是P-gp、BCRP、MRP1和MRP2。这些外排转运蛋白具有神经保护作用，限制神经毒素进入大脑；然而，它们也可能限制许多治疗药物的进入并导致中枢神经系统耐药性。对控制脑毛细血管内皮中 ABC 外排转运蛋白的表达和活性的几种调控途径的表征已经形成了一个新的共识，即这些过程是复杂的并且包含多种细胞和分子元件。 ABC 外排转运蛋白表达和/或活性的改变发生在多种神经系统疾病中。在这里，我们回顾了调节 P-gp、BCRP、MRP1 和 MRP2 表达和转运活性的信号通路，以及它们的表达/活性在神经系统疾病中的变化。
The strength of the blood-brain barrier (BBB) in providing protection to the central nervous system from exposure to circulating chemicals is maintained by tight junctions between endothelial cells and by a broad range of transporter proteins that regulate exchange between CNS and blood. The most important transporters that restrict the permeability of large number of toxins as well as therapeutic agents are the ABC transporters. Among them, P-gp, BCRP, MRP1 and MRP2 are the utmost studied. These efflux transporters are neuroprotective, limiting the brain entry of neurotoxins; however, they could also restrict the entry of many therapeutics and contribute to CNS pharmacoresistance. Characterization of several regulatory pathways that govern expression and activity of ABC efflux transporters in the endothelium of brain capillaries have led to an emerging consensus that these processes are complex and contain several cellular and molecular elements. Alterations in ABC efflux transporters expression and/or activity occur in several neurological diseases. Here, we review the signaling pathways that regulate expression and transport activity of P-gp, BCRP, MRP1 and MRP2 as well as how their expression/activity changes in neurological diseases.