阿尔茨海默病（AD）的发病与Aβ聚集有直接关系。热休克蛋白70（HSP70）能降低Aβ错误折叠和聚集，减轻神经元损伤。研究发现PPARγ激动剂可激活热休克因子, 提高HSP70的表达。因此我们设想，如果能通过PPARγ配体激活PPARγ进而提高HSP70的表达，对于AD的治疗具有重要的价值。我们前期研究发现姜黄素是PPARγ的天然激动剂，预实验研究发现姜黄素可抑制Aβ聚集和诱导小鼠海马HSP70的表达，推测姜黄素治疗AD可能与激活PPARγ-HSP70路径有关。本项目拟采用蛋白质组学进一步鉴定和验证姜黄素对HSP70的诱导作用，然后RNAi分别沉默PPARγ和HSP70表达，研究PPARγ-HSP70路径是否存在，同时探讨该路径在抑制Aβ聚集及抑制Tau蛋白磷酸化中的作用。最后在转基因AD小鼠模型中分别抑制PPARγ和HSP70以验证姜黄素对其治疗作用与PPARγ-HSP70路径有关。

Aβ aggregation has a direct relationship with the pathogenesis of Alzheimer's disease (AD). Heat shock protein 70 (HSP70) can reduce Aβ misfolding and aggregation, reduce neuronal damage. The study found that PPARγ agonist can activate heat shock factor, increase the expression of HSP70. Therefore, we envisaged through PPARγ ligands activate PPARγ thereby increasing the expression of HSP70 has important value for the treatment of AD. Our previous study found that curcumin is the natural agonist of PPARγ, pre-experimental study found that curcumin can inhibit Aβ aggregation and induce expression of mouse hippocampus HSP70, suggesting that curcumin may treat AD through the activation of PPARγ-HSP70 pathway. The project intends to use proteomics to identify and validate the induction of curcumin on HSP70. Then RNAi silence expression of PPARγ and HSP70 respectively. Validate whether the PPARγ-HSP70 pathway exists, and at the same time to explore it's role of inhibition of Aβ aggregation and phosphorylation of Tau protein. Finally, inhibition of PPARγ and HSP70 in transgenic mouse models of AD to verify therapeutic role of curcumin and the relationship with PPARγ-HSP70 pahtway.