小胶质细胞NF-κB激活在中枢神经系统疾病中发挥重要作用。文献报道Numbl可以分别与TRAF6、TAB2结合调节NF-κB的活性,但对Numbl、TRAF6及TAB2是否能形成三元复合物，并调节NF-κB的活性及小胶质细胞激活尚无研究。本课题拟首先在小胶质细胞中证明Numbl、TRAF6与TAB2可以形成三元复合物；接着分析在小胶质细胞炎性活化中，上述三元复合物对TRAF6泛素化及NF-κB激活的影响，并通过干预小胶质细胞中上述三种分子的表达及相互作用，分析三元复合物的形成对小胶质细胞炎性激活的影响；最后在整体神经炎症模型中，干预上述三元复合体的形成，验证其是否通过调节NF-κB的活性，对中枢神经系统炎症反应的产生影响。研究结果可为中枢神经系统疾病的治疗提供理论依据及分子靶点。

The activation of NF-κB in microglia played an essential role in central nerve system development. It has reported Numbl may affect NF-κB activation via interaction with TRAF6 or TAB2, but whether Numbl form a ternary complex with TAB2 and TRAF6, and affect NF-κB signal transduction and microglia activation were still unknown. In this projected, we may firstly proved Numbl may form ternary complex with TRAF6 and TAB2 in microglia. And then we may analysis the role of the complex in TRAF6 ubquination, NF-κB activation. At the same time, we will detect the role of Numbl-TRAF6-TAB2 complex in microglia activation via affecting these genes expression. At last, we may detected the role of the ternary complex in central never system inflammation by affecting it formation in vivo. All the data may support basic theory and molecular target for therapy in central never system disease.