线粒体功能障碍是Alzheimer's disease (AD)的一个重要病理特征。线粒体自噬是细胞内维持线粒体质量的重要机制，但其在AD中调控机制仍不清楚。L1-70是由髓鞘碱性蛋白(MBP）酶切细胞粘附因子L1（L1 CAM）产生的70 kD片段，其在线粒体上表达。我们前期发现L1-70在AD模型小鼠脑内表达降低，并通过其胞内段的LIR（LC3 interaction region）位点与LC3结合。过表达L1-70导致线粒体片段化，线粒体蛋白TOMM20水平下调，同时含线粒体的自噬小体增加，提示L1-70能诱导线粒体自噬；另外，过表达L1-70能挽救CCCP诱导的线粒体损伤。因此推测L1-70可能作为一个新的线粒体自噬受体参与AD的病理进程。本课题拟分析L1-70对线粒体自噬的调控作用，阐明其在AD病理发展中的作用和机制，为理解线粒体自噬在AD的病理作用和分子机制提供重要的参考依据。

Accumulation of damaged mitochondria is one of key pathological hallmarks of Alzheimer's disease (AD). Mitophagy plays essential roles in maintaining mitochondrial quality. L1-70 is generated from the cleavage of full-length L1CAM by myelin basic protein (MBP) and is expressed in mitochondria. However, the underling mechanisms of mitophagy and regulation in AD are still unclear. Our preliminary data have shown L1-70 level is decreased in the brains of AD transgenic mice. L1CAM interacted with LC3, a marker protein of autophagosome, through its LIR (LC3 interaction region). Overexpression of L1-70 caused fragmentation of mitochondria, reduced levels of mitochondrial protein TOMM20 and increased numbers of mitophagosomes, and also rescued mitochondrial dysfunction caused by CCCP. These data suggest L1-70 may be a novel mitophagy receptor, and L1-70-mediated mitophagy play essential roles in AD pathogenesis. We here in this project aim to verify the regulation of L1-70 on mitophagy and further elucidate its roles and mechanisms in the pathogenesis of AD. Our study will provide important data for understanding the role and molecular mechanisms of mitophagy in AD pathology.