Overcoming the blood–brain barrier (BBB) to enable the treatment of central nervous system (CNS) diseases is an active field of research. Modulating or opening the tight junctions (TJs) in brain endothelial cells is one method to enable a range of small-molecular-weight drugs to cross the BBB via the paracellular route. Over the past 2 decades, the molecular understanding of TJ proteins in the BBB has significantly improved, and several agonists and antagonists have been tested for modulation of the TJs. In this review, we discuss the composition of TJ proteins in the BBB and introduce indirect pharmacological TJ modulators, which target regulators of TJ proteins, and direct TJ modulators, which can selectively inhibit functions of TJ proteins.

克服血脑屏障 (BBB) 以治疗中枢神经系统 (CNS) 疾病是一个活跃的研究领域。调节或打开脑内皮细胞中的紧密连接 (TJ) 是使一系列小分子量药物通过细胞旁途径穿过 BBB 的一种方法。在过去的 20 年里，对 BBB 中 TJ 蛋白的分子理解有了显着提高，并且已经测试了几种激动剂和拮抗剂以调节 TJ。在这篇综述中，我们讨论了 BBB 中 TJ 蛋白的组成，并介绍了靶向 TJ 蛋白调节剂的间接药理学 TJ 调节剂和可以选择性抑制 TJ 蛋白功能的直接 TJ 调节剂。