Increasing evidence has placed inflammation and immune dysfunction at the center of the pathogenesis of Alzheimer's disease (AD). The mitochondrial protein translocator protein (18 kDa) (TSPO) is highly upregulated in microglia and astrocytes in response to inflammatory stimulation. However, the biological action of TSPO in the pathogenesis of AD has not been determined to date. In this study, we showed that TSPO expression was upregulated in brain tissues from AD patients and AD model mice. APP/PS1 mice lacking TSPO generated significantly higher levels of Aβ_1-40 and Aβ_1-42 peptides and more Aβ plaques, as well as enhanced microglial activation, in the brain. TSPO-deficient microglia cultured in vitro showed a significant decrease in the ability to phagocytose Aβ peptides or latex beads and generated more proinflammatory cytokines (TNF-α and IL-1β) in response to Aβ peptides. Our findings suggest that TSPO has protective functions against neuroinflammation and Aβ pathogenesis in AD. TSPO may be a potential drug target for the development of drugs that have therapeutic or preventive effects in neuroinflammatory diseases.

越来越多的证据已将炎症和免疫功能障碍置于阿尔茨海默病 (AD) 发病机制的中心。线粒体蛋白转运蛋白 (18 kDa) (TSPO) 在炎症刺激下在小胶质细胞和星形胶质细胞中高度上调。然而，迄今为止尚未确定 TSPO 在 AD 发病机制中的生物学作用。在这项研究中，我们发现 TSPO 表达在 AD 患者和 AD 模型小鼠的脑组织中上调。缺乏 TSPO 的 APP/PS1 小鼠产生显着更高水平的 Aβ _1-40和 Aβ _1-42肽和更多的 Aβ 斑块，以及增强的小胶质细胞激活，在大脑中。体外培养的 TSPO 缺陷小胶质细胞显示吞噬 Aβ 肽或乳胶珠的能力显着降低，并产生更多促炎细胞因子（TNF-α 和 IL-1β）以响应 Aβ 肽。我们的研究结果表明，TSPO 对 AD 中的神经炎症和 Aβ 发病机制具有保护作用。TSPO 可能是开发对神经炎症性疾病具有治疗或预防作用的药物的潜在药物靶点。