帕金森病（PD）是常见的神经变性疾病，其发病机制仍不明确。本课题组鉴定了新的PD相关基因-NUS1，前期研究发现NUS1缺失可导致多巴胺递质水平下降，NUS1可与突触囊泡蛋白SV2C相互结合。我们提出NUS1可能通过SV2C调控多巴胺能神经元中突触囊泡转运，介导多巴胺递质释放，参与PD的发病机制。本项目拟在前期研究基础上，从细胞水平、转基因小鼠水平，应用免疫共沉淀、GST Pull-down、免疫荧光、活细胞成像、透射电镜等技术，明确NUS1是否可与SV2C直接相互作用，明确NUS1是否可调控SV2C表达，探讨NUS1是否通过SV2C调控突触囊泡转运参与PD的发病机制。

Parkinson’s disease (PD) is a common neurodegenerative disorder, and the pathogenesis of PD remains largely elusive. Our group identified NUS1 as a new PD-related gene. Our preliminary study with the NUS1 knock out Drosophila and mouse model demonstrated that the loss of NUS1 could reduce the dopamine level. Besides, we identified synaptic vesicle protein 2C (SV2C) as one of proteins interacting with NUS1. We propose that NUS1 could mediate the synaptic vesicle trafficking and dopamine release through SV2C and play a role in the pathogenesis of PD. On the basis of previous studies, this project aims to study the molecular mechanism of NUS1 regulating the synaptic vesicle trafficking through SV2C by Co-immunoprecipitation, GST pull-down, Western Blot, Immunofluorescence, live cell image and electron microscopy in vitro and in vivo.