前期研究显示，红花黄色素（SY）可改善痴呆小鼠、大鼠学习记忆缺失，减轻Aβ的神经元毒性作用并降低磷酸化Tau蛋白表达。提示SY的抗阿尔茨海默病（AD）作用可能与其调节AD的初始致病因子-Tau蛋白异常磷酸化和Aβ沉积有关。在此课题中，我们以Tau蛋白和Aβ为研究靶点，采用Aβ1-42海马注射致大鼠痴呆模型及APP/PS1转基因小鼠模型，观察SY对不同磷酸化位点Tau蛋白及其上游的蛋白激酶(GSK-3β和CDK5)和磷酸酶(PP2A)的调节作用，观察SY对Aβ合成、α分泌酶、β分泌酶等及其上游信号转导蛋白(PKC、MAPK等)的调控作用；在细胞水平上我们将采用冈田酸诱导的Tau蛋白过度表达模型和稳定转染APP695的神经母细胞瘤细胞株, 并使用不同的信号转导蛋白抑制剂进一步阐明SY对Tau蛋白磷酸化和APP加工过程的调节机制，希望能寻找一种可延缓AD发病进程的药物。

Previous studies showed that safflor yellow (SY) improved the learning and memory deficits in the dementia mice and rats and attenuated the neurotoxicity of Aβ and lowed the expression of phosphorylated Tau protein. The results suggested that the anti-Alzheimer's disease effect of SY may be related to regulate the initial pathogenic factor of Alzheimer's disease-Tau protein hyperphosphorylation and Aβ deposition. On this topic, we will take the Tau protein and Aβ as the research target, using Aβ1-42 hippocampus-injected rats and APP/PS1 transgenic mice to further observe the regulatory role of SY on the different phosphorylated sites Tau protein and its upstream protein kinase (GSK-3β and CDK5) and phosphatase (PP2A). In APP/PS1 transgenic mice, we will observe the regulatory effects of SY on Aβ synthesis, α-secretase enzyme, β-secretase enzyme and its upstream signal transduction proteins (PKC, MAPK, etc.). At the cellular level, okadaic acid-induced hyperphosphorylated tau model and neuroblastoma SK-N-SH cells over-expressing human APP695 are used to further investigate the effect of SY on Tau phosphorylation and APP processing. In addition, various signal transduction inhibitors will be applied to elucidate the regulatory mechanism of SY on Tau phosphorylation and APP processing. This project is expected to find a drug to delay the process of Alzheimer's disease.