BAG5（BCL2-associated athanogene 5）是BAG蛋白家族中唯一包含多个BAG结构域的蛋白，在进化上保守。目前研究表明BAG5可能参与调控多个帕金森病致病基因的生理功能，其在PD发病机制中的作用仍存在争议。本研究组前期在细胞学水平上研究发现PINK1和BAG5存在直接相互作用，BAG5可通过减少PINK1的泛素化水平，延长PINK1的降解半衰期，起到稳定PINK1的作用。但在模式生物上BAG5是否存在对PINK1的调控作用仍不清楚。本研究拟在前期研究基础上，对已获得的BAG5基因敲除小鼠模型进行鉴定，明确BAG5敲除小鼠中多巴胺能神经元是否对MPTP更易感，在此基础上探讨BAG5基因敲除对PINK1蛋白稳定性的影响，进一步探讨这种影响对多巴胺能神经元细胞线粒体功能、自噬及细胞凋亡的影响，深入探讨BAG5调控PINK1蛋白稳定性在帕金森病发病机制中的作用。

BAG5（BCL2-associated athanogene 5）is the only member of BAG (Bcl-2 associated athanogene) which has several BAG domains and is conserved in evolution. It was reported that BAG5 might regulate several pathogenic genes of Parkinson’s disease (PD) in their physiological function process. There is still controversy in the role of BAG5 in the pathogenesis of PD. In our previous studies on cytological level, we found BAG5 can directly interact with PINK1 and BAG5 protein prolonged the half-lives of PINK1 by inhibiting the ubiquitination of PINK1. It’s still not clear whether BAG can regulate PINK1 stability in model organism. On the basis of our preliminary study, we will verify the BAG5 knock-out mouse (BAG5-/-) which we have already got in this study, and then study whether the dopaminergic neurons in this knock-out mouse are more susceptible to MPTP. We will investigate the influence of PINK1 stability on the BAG5 knock-out model, and then approach whether this influence will cause mitochondria dysfunction, autophagy dysfunction, and cell apoptosis which are lethal to dopaminergic neurons. The main objective of this study is to further study the role of PINK1 stability regulated by BAG5 in the pathogenesy of Parkinson's disease.