Neuroligin-1是位于兴奋性突触后膜上的一种神经粘附分子，在突触的形成、发育、成熟和突触可塑性调控中发挥至关重要的作用。Aβ诱导的神经炎症可通过影响neuroligin-1的表观遗传修饰，减少neuroligin-1的表达，并最终损伤突触的结构和功能。我们的前期工作表明，雷公藤内酯醇能抑制阿尔茨海默病（AD）脑内Aβ诱导的免疫炎症反应，并具有明确的突触保护作用。但雷公藤内酯醇究竟通过何种机制发挥其突触保护作用还不清楚。本项目拟用免疫细胞化学染色、western blot、实时定量PCR、DNA甲基化免疫共沉淀、染色质免疫共沉淀、免疫共沉淀等技术，观察雷公藤内酯醇及其衍生物雷公藤氯内酯醇对AD动物模型（APP/PS1双转基因AD模型小鼠）和AD细胞模型海马神经元neuroligin-1表达的影响并探讨其表观遗传调控机制，以期进一步阐明其相应的突触保护作用的靶点。

Neuroligin-1 is a postsynaptic cell-adhesion protein specific for excitatory synapses and plays critical roles in synapse morphogenesis, maintenance and plasticity. Beta-amyloid protein(Aβ)-induced neuroinflammation decreased neuroligin-1 expression by modulating the epigenetic modification of neuroligin-1 promoter, underlying Aβ-induced synaptic impairment. Our previous work has shown that triptolide can inhibit Aβ-induced neuroinflammation in Alzheimer’s disease(AD) brain and has a clear synaptic protective effect. However, the precise mechanism for the synaptic protective effect of triptolide remains unclear. In this project, immunocytochemical staining, western blot, real-time quantitative PCR, methylated DNA immunoprecipitation, chromatin immunoprecipitation and co-immunoprecipitation will be used to observe the effect of triptolide and its derivative tripchlorolide on neuroligin-1 expression in hippocampal neurons of AD animal model (APPswe/PS1dE9 transgenic mice) and AD cellular model and to explore their epigenetic regulatory mechanisms, hoping to further elucidate the target of their synaptic protective effect.