phkineticaФармакокинетика и ФармакодинамикаPharmacokinetics and Pharmacodynamics2587-78362686-8830ООО «Издательство ОКИ»10.24411/2587-7836-2018-10026phkinetica-72Research ArticleОБЗОРЫREVIEWSТранслокаторный белок TSPO 18 кДа и его лиганды: перспективный подход к созданию новых нейропсихотропных средствTranslocator protein TSPO 18 kDa and its ligands: a promising approach to the creation of new neuropsychotropic drugМокровГригорий ВладимировичMokrovG. V.g.mokrov@gmail.comДееваОльга АлексеевнаDeevaO. A.noemail@neicon.ruЯрковаМилада АльнордовнаYarkovaM. A.noemail@neicon.ruГудашеваТатьяна АлександровнаGudashevaT. A.noemail@neicon.ruСереденинСергей БорисовичSeredeninS. B.noemail@neicon.ruФГБНУ «НИИ фармакологии имени В.В. Закусова»РоссияFSBI «Zakusov Institute of Pharmacology»Russian Federation20180611201804327Copyright © Мокров Г.В., Деева О.А., Яркова М.А., Гудашева Т.А., Середенин С.Б., 20182018Мокров Г.В., Деева О.А., Яркова М.А., Гудашева Т.А., Середенин С.Б.Mokrov G.V., Deeva O.A., Yarkova M.A., Gudasheva T.A., Seredenin S.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacokinetica.ru/jour/article/view/72

В 2018 году исполняется 41 год с момента открытия Браэстрап и Сквирес транслокаторного белка TSPO 18 кДа, известного до 2006 года под названием «периферический бензодиазепиновый рецептор» (PBR). За это время были подробно исследованы функции этого рецептора, который является важнейшим компонентом наружной мембраны митохондрий. Одной из ключевых функций TSPO является перенос холестерина от внешней к внутренней мембране митохондрий, что является лимитирующей стадией в синтезе нейростероидов. Кроме того, TSPO задействован в транспорте порфиринов, митохондриальном дыхании, открытии митохондриальных пор, апоптозе и пролиферации клеток. Настоящий обзор посвящён рассмотрению современных представлений о структуре TSPO, механизме его участия в нейростероидогенезе и эндогенных и синтетических лигандах TSPO. Особый акцент сделан на анализе подходов к дизайну синтетических лигандов и их нейропсихотропной активности in vitro и in vivo. Представленный обзор демонстрирует перспективность конструирования новых нейропсихотропных средств в ряду лигандов TSPO.

Resume. It is 41 years in 2018 since Braestrup and Squires opened translocator protein 18 kDa TSPO, known until 2006 as the peripheral benzodiazepine receptor (PBR). The functions of this receptor, which is one of the most important component of the outer mitochondrial membrane, have been studied in detail during this time. One of the key functions of TSPO is the transfer of cholesterol from the outer to the inner membrane of mitochondria, which is the limiting step in the synthesis of neurosteroids. In addition, TSPO is involved in porphyrin transport, mitochondrial respiration, the opening of mitochondrial pores, apoptosis and cell proliferation. This review presents the modern views on the structure of TSPO, the mechanism of it participation in neurosteroidogenesis and the endogenous and synthetic ligands of TSPO. Particular emphasis is placed on the analysis of approaches to the design of synthetic ligands and their neuropsychotropic activity in vitro and in vivo. This review demonstrates the prospects of new neuropsychotic drugs design among TSPO ligands.

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The authors declare that there are no conflicts of interest present.