ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery.

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Pharmacological Reviews Pub Date : 2023-09-01 Epub Date: 2023-03-27 DOI:10.1124/pharmrev.120.000025
Julia A Schulz, Anika M S Hartz, Björn Bauer
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引用次数: 0

Abstract

The drug efflux transporters ABCB1 and ABCG2 at the blood-brain barrier limit the delivery of drugs into the brain. Strategies to overcome ABCB1/ABCG2 have been largely unsuccessful, which poses a tremendous clinical problem to successfully treat central nervous system (CNS) diseases. Understanding basic transporter biology, including intracellular regulation mechanisms that control these transporters, is critical to solving this clinical problem.In this comprehensive review, we summarize current knowledge on signaling pathways that regulate ABCB1/ABCG2 at the blood-brain barrier. In Section I, we give a historical overview on blood-brain barrier research and introduce the role that ABCB1 and ABCG2 play in this context. In Section II, we summarize the most important strategies that have been tested to overcome the ABCB1/ABCG2 efflux system at the blood-brain barrier. In Section III, the main component of this review, we provide detailed information on the signaling pathways that have been identified to control ABCB1/ABCG2 at the blood-brain barrier and their potential clinical relevance. This is followed by Section IV, where we explain the clinical implications of ABCB1/ABCG2 regulation in the context of CNS disease. Lastly, in Section V, we conclude by highlighting examples of how transporter regulation could be targeted for therapeutic purposes in the clinic. SIGNIFICANCE STATEMENT: The ABCB1/ABCG2 drug efflux system at the blood-brain barrier poses a significant problem to successful drug delivery to the brain. The article reviews signaling pathways that regulate blood-brain barrier ABCB1/ABCG2 and could potentially be targeted for therapeutic purposes.

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血脑屏障中的 ABCB1 和 ABCG2 调节:改善脑部给药的潜在新靶点。
血脑屏障上的药物外排转运体 ABCB1 和 ABCG2 限制了药物进入大脑。克服 ABCB1/ABCG2 的策略大多不成功,这给成功治疗中枢神经系统(CNS)疾病带来了巨大的临床难题。在这篇综述中,我们总结了目前有关血脑屏障 ABCB1/ABCG2 信号通路的知识。在第一节中,我们概述了血脑屏障研究的历史,并介绍了 ABCB1 和 ABCG2 在其中发挥的作用。第二节中,我们总结了为克服血脑屏障 ABCB1/ABCG2 外流系统而测试的最重要策略。第三节是本综述的主要部分,我们将详细介绍已确定的在血脑屏障上控制 ABCB1/ABCG2 的信号通路及其潜在的临床意义。随后,我们将在第四部分解释 ABCB1/ABCG2 在中枢神经系统疾病中的临床意义。最后,在第五部分中,我们将举例说明如何在临床中针对治疗目的调控转运体。意义声明:血脑屏障上的 ABCB1/ABCG2 药物外流系统对成功将药物输送到大脑构成了重大问题。文章回顾了调控血脑屏障 ABCB1/ABCG2 的信号通路,这些信号通路有可能成为治疗目的的靶点。
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
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
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