神经元线粒体凋亡途径是术后认知功能障碍（POCD）的发生机制之一，其上游机制不清。我们前期发现：脑内α-突触核蛋白（α-syn）寡聚化及其伴侣分子14-3-3蛋白β/α亚型在多个脑区的显著下调，可能与POCD有关。14-3-3参与α-syn寡聚化之前的磷酸化，后者又可反向抑制14-3-3的转录；鉴于二者均参与凋亡的调控，故推测二者的交互作用失衡在POCD线粒体凋亡途径中可能扮演重要角色。本项目拟通过探究麻醉/手术后α-syn与14-3-3的交互作用，明确α-syn寡聚化与线粒体凋亡途径的关系；在此基础上，利用课题组前期已构建的抗坏血酸过氧化物酶（APEX）蛋白标记技术，在线粒体特定部位筛选出与α-syn具有直接作用的蛋白质组，并通过互作蛋白质组学技术明确麻醉/手术后α-syn调控线粒体凋亡途径的分子机制。研究结果将有助于解析线粒体介导的神经元凋亡及其调控机制，为POCD的防治提供潜在靶点。

Neuronal mitochondrial apoptosis pathway is one of the mechanisms of postoperative cognitive impairment (POCD). Nevertheless, the upstream signaling of mitochondria damage and cell apoptosis remains elusive. Our previous studies found that POCD may be related to the oligomerization of α-synuclein (α-syn) in the brain, while its chaperone 14-3-3β/α was significantly down-regulated in multiple brain regions. 14-3-3 protein is involved in the phosphorylation of α-syn prior to its oligomerization, and this pathological change in turn inhibits the transcription of 14-3-3 protein. Since both α-syn and 14-3-3 proteins are involved in the regulation of neuronal apoptosis, we speculate that the interaction between α-syn and 14-3-3 proteins may play an important role in the regulation of mitochondrial apoptosis pathway after anesthesia/surgery. In this study, the interactions between α-syn and 14-3-3 proteins after challenges of anesthesia/surgery are to be observed, to clarify the relationship between the oligomerization of α-syn and mitochondrial apoptosis pathway. Furthermore, the protein interactome of α-syn in specific mitochondrial compartments will be screened out by using the ascorbate peroxidase (APEX)-based labeling method we previously constructed. The effector molecules of α-syn regulating mitochondrial apoptosis pathway after challenges of anesthesia/surgery, are to be revealed by techniques for interaction proteomics. The results of this study will help to reveal the mitochondrial mediated neuronal apoptosis and its regulatory mechanisms, providing potential targets for the prevention and treatment of POCD.