Caballero Beatriz, Veenman Leo, Gavish Moshe
Department of Molecular Pharmacology, Technion-Israel Institute of Technology, Faculty of Medicine, Haifa, Israel.
Recent Pat Endocr Metab Immune Drug Discov. 2013 May;7(2):86-101. doi: 10.2174/1872214811307020002.
The 18 kDa translocator protein (TSPO) is able to modulate several mitochondria-related cell death processes due to close association with proteins and other molecules involved to the mitochondrial permeability transition pore. In this way, herein we review cell death mechanisms targeting mitochondria, including programmed cell death type I, II and III. Several proteins involved in these cell death processes and with a possible interplay with the TSPO are also discussed including the voltage dependent anion channel, the adenine nucleotide transporter, cardiolipin, and the Bcl-2 family proteins. Noteworthy, TSPO has been also implicated in various other functions including mitochondrial respiration, immune and phagocytic host-defense response, microglial activation, inflammation, cell growth and differentiation, cancer, cell proliferation, ischemia, and mental and neuropathological disorders. We focused in recent studies of the TSPO particularly on cancer and neurodegeneration, thus presenting the TSPO as a core element in the role of mitochondria in diseases and related processes. Clinical benefit may be attainable by increasing pharmacological knowledge related to the TSPO. Recent patents typically relate to diagnosis and treatment of TSPO-related pathological conditions including cancer, and inflammatory conditions, as well as disorders associated with central nervous system, such as neurodegeneration, convulsions, anxiety, mental disorders, and dementia.
18 kDa转位蛋白(TSPO)由于与参与线粒体通透性转换孔的蛋白质和其他分子密切相关,能够调节多种与线粒体相关的细胞死亡过程。通过这种方式,我们在此综述针对线粒体的细胞死亡机制,包括程序性细胞死亡I型、II型和III型。还讨论了参与这些细胞死亡过程并可能与TSPO相互作用的几种蛋白质,包括电压依赖性阴离子通道、腺嘌呤核苷酸转运体、心磷脂和Bcl-2家族蛋白。值得注意的是,TSPO还涉及各种其他功能,包括线粒体呼吸、免疫和吞噬宿主防御反应、小胶质细胞激活、炎症、细胞生长和分化、癌症、细胞增殖、缺血以及精神和神经病理障碍。我们重点关注了TSPO的最新研究,特别是在癌症和神经退行性变方面,从而将TSPO呈现为线粒体在疾病和相关过程中作用的核心要素。通过增加与TSPO相关的药理学知识可能会获得临床益处。近期专利通常涉及TSPO相关病理状况的诊断和治疗,包括癌症、炎症状况以及与中枢神经系统相关的疾病,如神经退行性变、惊厥、焦虑、精神障碍和痴呆。