阿尔兹海默病(AD)患者存在严重的成年神经再生障碍，调控机理尚不清楚。轴突导向因子Semaphorin3A(Sema3A)在AD病理区的表达显著上调，我们前期的研究初步发现，Sema3A能够抑制成年神经干细胞(aNSCs)的增殖，进而降低神经再生功能，但分子机制不明。有报道Sema3A具有调控细胞有丝分裂纺锤体的定位功能，且Sema3A下游分子GSK3β与中心粒结构有关，推测Sema3A很可能通过影响aNSCs分裂骨架的对称性，调控AD神经再生。本项目在利用光转换荧光蛋白和胚胎电转对aNSC进行特异性标记的基础上，探索(1)Sema3A在调控aNSC分裂过程中的上游调控机理；(2)Sema3A调控aNSC分裂过程中的介导分子；(3) Sema3A引起的aNSCs分裂模式的变化对AD神经再生的影响。通过以上内容的研究，揭示AD成年神经再生障碍的分子机理，以期为AD的早期诊断提供标志物。

There is a serious defect in adult neurogenesis of Alzheimer’s disease (AD) individuals. However, the regulatory mechanism is still unclear. Semaphorin3A, an axon guidance factor, is significantly over-expressed in pathologies of AD. We previously found that Sema3A inhibited the proliferation of adult neural stem cells and which further resulted in the decrease of adult neurogenesis, but the specific mechanism is unkown. Research reports that Sema3A has critical roles in mitotic spindle positioning, and the downstream molecule of Sema3A signal pathway-GSK3β has close relationship with structural integrity of centrosome. These suggest that Sema3A probably function as a regulator in AD adult neurogenesis by affecting the symmetry of adult neural stem cells (aNSCs) division skeleton. Here, we will explore the upstream regulatory mechanism in aNSC division process modulated by Sema3A and the interactive molecules during this process, as well as the effects of aNSCs’ division type on AD adult neurogenesis induced by Sema3A. The findings from these studies will unravel the molecular mechanism of defect in AD adult neurogenesis and these will be helpful to explore the early biomarkers for evaluating the progress of AD.