Pharmacology and Neuroscience, University of North Texas Health Science Center, Institute for Healthy Aging, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, United States.
Curr Alzheimer Res. 2020;17(1):3-15. doi: 10.2174/1567205017666200217105950.
Translocator Protein (18 kDa) (TSPO) is a mitochondrial protein that locates cytosol cholesterol to mitochondrial membranes to begin the synthesis of steroids including neurotrophic neurosteroids. TSPO is abundantly present in glial cells that support neurons and respond to neuroinflammation. Located at the outer membrane of mitochondria, TSPO regulates the opening of mitochondrial permeability transition pore (mPTP) that controls the entry of molecules necessary for mitochondrial function. TSPO is linked to neurodegenerative Alzheimer's Disease (AD) such that TSPO is upregulated in the brain of AD patients and signals AD-induced adverse changes in brain. The initial increase in TSPO in response to brain insults remains elevated to repair cellular damages and perhaps to prevent further neuronal degeneration as AD progresses. To exert such protective activities, TSPO increases the synthesis of neuroprotective steroids, decreases neuroinflammation, limits the opening of mPTP, and reduces the generation of reactive oxygen species. The beneficial effects of TSPO on AD brain are manifested as the attenuation of neurotoxic amyloid β and mitochondrial dysfunction accompanied by the improvement of memory and cognition. However, the protective activities of TSPO appear to be temporary and eventually diminish as the severity of AD becomes profound. Timely treatment with TSPO agonists/ligands before the loss of endogenous TSPO's activity may promote the protective functions and may extend neuronal survival.
转位蛋白（18kDa）（TSPO）是一种位于线粒体的蛋白质，它将细胞质中的胆固醇转运到线粒体膜上，开始合成包括神经营养性神经甾体在内的甾体。TSPO 在支持神经元的神经胶质细胞中大量存在，并对神经炎症做出反应。TSPO 位于线粒体的外膜上，调节线粒体通透性转换孔（mPTP）的开放，控制进入线粒体功能所需的分子。TSPO 与神经退行性阿尔茨海默病（AD）有关，TSPO 在 AD 患者的大脑中上调，并发出 AD 诱导的大脑不良变化信号。TSPO 对大脑损伤的最初增加仍然升高，以修复细胞损伤，也许可以防止 AD 进展过程中进一步的神经元退化。为了发挥这种保护作用，TSPO 增加了神经保护甾体的合成，减少了神经炎症，限制了 mPTP 的开放，并减少了活性氧的产生。TSPO 对 AD 大脑的有益作用表现为神经毒性淀粉样β和线粒体功能障碍的减弱，同时记忆力和认知能力得到改善。然而，TSPO 的保护作用似乎是暂时的，随着 AD 的严重程度加深而逐渐减弱。在内源性 TSPO 活性丧失之前，及时用 TSPO 激动剂/配体进行治疗可能会促进保护功能，并延长神经元的存活。
