Zakusov Research Institute of Pharmacology, 125315, Moscow, Russian Federation.
Curr Pharm Des. 2021;27(2):217-237. doi: 10.2174/1381612826666200903122025.
In 2020, it is already 43 years since Braestrup and Squires discovered 18 kDa translocator protein (TSPO), known until 2006 as "peripheral benzodiazepine receptor". During this time, the functions of this receptor, which is located on the outer membrane of mitochondria, were studied in detail. One of the key functions of TSPO is the transfer of cholesterol from the outer to the inner mitochondrial membrane, which is the limiting stage in the synthesis of neurosteroids. TSPO is also involved in the transport of porphyrins, mitochondrial respiration, the opening of mitochondrial pores, apoptosis and cell proliferation. This review presents current information on the structure of TSPO, the mechanism of its participation in neurosteroidogenesis, as well as endogenous and synthetic TSPO ligands. Particular emphasis is placed on the analysis of approaches to the design of synthetic ligands and their neuropsychotropic activity in vitro and in vivo. The presented review demonstrates the promise of constructing new neuropsychotropic drugs in the series of TSPO ligands.
2020 年，Braestrup 和 Squires 发现 18 kDa 移位蛋白（TSPO）已经过去了 43 年，直到 2006 年，该蛋白才被称为“外周苯二氮䓬受体”。在此期间，详细研究了这种位于线粒体外膜上的受体的功能。TSPO 的一个关键功能是将胆固醇从线粒体的外膜转移到内膜，这是神经甾体合成的限速阶段。TSPO 还参与了卟啉的转运、线粒体呼吸、线粒体孔的打开、细胞凋亡和细胞增殖。这篇综述介绍了 TSPO 的结构、参与神经甾体生成的机制以及内源性和合成 TSPO 配体的最新信息。特别强调了对合成配体设计方法及其在体外和体内的神经精神活性的分析。所呈现的综述表明，在 TSPO 配体系列中构建新型神经精神药物具有广阔的前景。
