β-淀粉样蛋白（Aβ）聚集是阿尔茨海默病(AD)核心发病机制，星形胶质细胞能够抑制Aβ的聚集，但机制不详。星形胶质细胞内源性B-晶状体蛋白（Cryab）能够阻止Aβ聚集。我们发现，激活星形胶质细胞a7胆碱能受体（a7nAChRs）能够显著增强星形胶质细胞对Aβ聚集的抑制，但具体调控机制不清楚。在预实验中发现：a7nAChRs的激活引起细胞内钙增加和Cryab上调，而且Cryab上调依赖于细胞内钙水平升高和钙调蛋白（CaM）活性增强。因此，我们推测"激活星形胶质细胞的a7 nAChRs，引起细胞内钙水平和CaM升高，从而上调Cryab，促进Cryab对Aβ蛋白聚集的抑制"是星形胶质细胞a7nAChRs抑制Aβ聚集的新机制。本课题拟制备a7nAChRs敲除、AD动物模型和星形胶质细胞，应用siRNA，Cryab转染等技术，从整体-细胞层次证明我们的假说。本研究将为AD的防治提供新的思路和靶点。

Astrocytic alpha7 nicotinic receptors inhibit βamyloid aggregation via upregulation endogenous Cryab The aggregation of β-amyloid (Aβ) play an important role in the pathogenesis of Alzheimer's disease (AD). Astrocytes can significantly inhibit the aggregation of Aβ. However, the mechanism is unknown. B-crystallin (Cryab), one astrocytic endogenous protein, has been shown to inhibit Aβ aggregation. In our previous studies, we found the activation of astrocytic alpha7 nicotinic receptors (nAChRs) can significantly enhance the ability of astrocytes to inhibit Aβaggregation. However, the underline mechanism is still unknown. Our recently preliminary data showed that the activation of astrocytic alpha7 nAChRs can induce the upregulations of intracellular Calcium as well as Cryab. Furthermore, the upregulations of Cryab is dependent on the level of Calcium and the activity of Calmodulin (CaM). Based on our preliminary data, we hypothesized that the activation of astrocytic alpha7 nAChRs can firstly induce increased Calcium and CaM activity, then induce the upregulation of Cryab. The increased Cryab enhance the inhibition of Aβ aggregation. Our hypothesis will be tested in several transgenic animal and cell culture models by using Cryab SiRNA and gene transfection techniques. Our project will provide new ideas and therapeutic targets for AD treatment.