Institute of Clinical Physiology, National Research Council of Italy, CNR Research Area, Via G. Moruzzi 1, Pisa 56124, Italy.
Department of Pharmacy, University of Pisa, Via Bonanno 6, Pisa 56126, Italy.
J Med Chem. 2024 Jan 11;67(1):17-37. doi: 10.1021/acs.jmedchem.3c01716. Epub 2023 Dec 19.
Mitochondria dysfunctions are typical hallmarks of cardiac disorders (CDs). The multiple tasks of this energy-producing organelle are well documented, but its pathophysiologic involvement in several manifestations of heart diseases, such as altered electromechanical coupling, excitability, and arrhythmias, is still under investigation. The human 18 kDa translocator protein (TSPO) is a protein located on the outer mitochondrial membrane whose expression is altered in different pathological conditions, including CDs, making it an attractive therapeutic and diagnostic target. Currently, only a few TSPO ligands are employed in CDs and cardiac imaging. In this Perspective, we report an overview of the emerging role of TSPO at the heart level, focusing on the recent literature concerning the development of TSPO ligands used for fighting and imaging heart-related disease conditions. Accordingly, targeting TSPO might represent a successful strategy to achieve novel therapeutic and diagnostic strategies to unravel the fundamental mechanisms and to provide solutions to still unanswered questions in CDs.
线粒体功能障碍是心脏疾病(CDs)的典型特征。这个产能细胞器的多项任务已有详细记录,但它在心脏病多种表现中的病理生理作用,如电机械偶联、兴奋性和心律失常的改变,仍在研究中。人类 18 kDa 转位蛋白(TSPO)是一种位于线粒体外膜的蛋白质,其表达在不同的病理条件下发生改变,包括 CDs,使其成为有吸引力的治疗和诊断靶点。目前,只有少数 TSPO 配体用于 CDs 和心脏成像。在本观点中,我们报告了 TSPO 在心脏水平的新兴作用,重点介绍了最近关于用于对抗和成像与心脏相关疾病的 TSPO 配体的发展的文献。因此,靶向 TSPO 可能代表着一种成功的策略,可以实现新的治疗和诊断策略,以揭示基本机制,并为 CDs 中仍未回答的问题提供解决方案。