Singh Priya, Singh Vijay Kumar, Gond Chandraprakash, Singh Deepika, Tiwari Anjani Kumar
Department of Chemistry, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, 226025, India.
Mol Divers. 2025 Jun;29(3):2639-2689. doi: 10.1007/s11030-024-10963-0. Epub 2024 Dec 4.
The translocator protein 18 kDa (TSPO) is a crucial external mitochondrial protein involved in cholesterol translocation, which is essential for steroid production. As a primary marker of neuroinflammation, TSPO has been implicated in the development and progression of various neurodegenerative and neuropsychiatric disorders. This review highlights the structural diversity of TSPO ligands, many of which have undergone modifications from selective central benzodiazepine receptor (CBR) ligands to enhance their affinity for TSPO. The paper discusses the significant advancements in the design of these ligands, emphasizing their binding efficacy and specificity. Additionally, it provides an update on the progress of several TSPO ligands that have advanced to clinical trials. The review aims to elucidate the structure-activity relationships (SAR) that govern the interaction between TSPO and its ligands, thereby offering insights into the development of new therapeutic agents targeting TSPO for the treatment of neuroinflammatory conditions. Overall, this work provided an update on previous finding and serves as a valuable resource for researchers in the field.
18 kDa转位蛋白（TSPO）是一种关键的线粒体外膜蛋白，参与胆固醇转运，这对类固醇生成至关重要。作为神经炎症的主要标志物，TSPO与多种神经退行性疾病和神经精神疾病的发生发展有关。本综述重点介绍了TSPO配体的结构多样性，其中许多配体已从选择性中枢苯二氮䓬受体（CBR）配体进行了修饰，以增强其对TSPO的亲和力。本文讨论了这些配体设计方面的重大进展，强调了它们的结合效力和特异性。此外，还提供了几种已进入临床试验的TSPO配体的进展更新。该综述旨在阐明支配TSPO与其配体相互作用的构效关系（SAR），从而为开发针对TSPO治疗神经炎症性疾病的新型治疗药物提供见解。总体而言，这项工作更新了以前的发现，是该领域研究人员的宝贵资源。
