线粒体功能障碍在阿尔茨海默病（AD）发病中起关键作用。我们前期研究表明，与AD相关的淀粉样前体蛋白（APP）过表达，可导致线粒体生物合成、线粒体动力学和线粒体自噬异常，引发线粒体功能障碍，但其中的机制尚不清楚。线粒体功能的发挥依赖于核编码蛋白导入线粒体，AD患者脑内APP阻塞TOM40蛋白导入通道，造成线粒体蛋白导入异常。基于酵母菌的最新研究报道，TOM70参与调节TOM40通道中阻塞蛋白的清除，即线粒体蛋白导入障碍反应（mitoCPR）。我们预实验发现AD动物模型脑内TOM70表达下调，但其参与AD发病的具体机制未见报道。据此，我们拟进一步研究TOM70通过调节TOM40介导的线粒体蛋白导入通路影响线粒体生物合成、线粒体动力学和线粒体自噬参与AD发病的机制，以期为AD的治疗研究提供新的靶点和思路。

Mitochondrial dysfunction plays a key role in the pathogenesis and progression of AD. Our previous studies showed that over expression of AD-associated mutant APP led to abnormalities of mitochondrial biosynthesis, mitochondrial dynamics and mitochondrial autophagy, leading to mitochondrial dysfunction. While the mechanism remains unclear. Mitochondrial function depends on the import of nuclear-encoded mitochondrial protein. APP combines with TOM40 to form a stable complex, which blocks the protein transport channel of TOM40 and causes mitochondrial protein import deficiency in AD。TOM70 is one of the key promoter proteins of mitochondrial compromised protein import response (mitoCPR). In our preliminary experiment, we found that the expression of TOM70 was down-regulated in AD mouse model. However the specific mechanism of its action in the pathogenesis of AD is still unknown. Therefore, we plan to detect the changes of TOM70 in different stages of AD and further study the specific mechanism of TOM70 involved in AD. We expected to provide new ideas for the search of new AD therapeutic targets.