磷酸化tau蛋白在神经元内异常聚集形成神经纤维缠结是阿尔茨海默病（AD）典型的病理改变之一，此过程与泛素-蛋白酶体系统（UPS）功能受损导致的异常蛋白质降解障碍密切相关。中医学认为，老年人脏腑功能虚弱，水湿津液不化，停聚为痰。痰浊蒙窍，神机失用是AD发病的核心环节。课题组前期研究发现，具有化痰开窍功效的远志散可以改善老年人记忆减退症状，提高认知水平，其益智作用在动物AD模型上也得到验证，能够降低海马中磷酸化tau蛋白的表达。基于此，我们提出假说：具有化痰开窍功效的远志散可能通过调控UPS蛋白降解途径，抑制磷酸化tau蛋白异常聚集，从而发挥治疗AD的作用”。本课题在中医理论指导下，围绕AD“磷酸化tau异常聚集”的发病机制，从UPS功能受损和磷酸化tau异常聚集的角度，以26S蛋白酶体为关键切入点，通过现代分子生物学技术和方法，探讨远志散治疗AD的作用机制，为化痰开窍法治疗AD提供科学依据。

Neurofibrillary tangles formed by phosphorylated tau protein abnormal aggregation in nerve cell, is one of the typical pathological changes of Alzheimer's disease (AD.) The process are closely related with function impairment of the Ubiquitin proteasome system (UPS) and resulting in abnormal protein degradation. The elders’ weak zang fu-organs, fluid can not transportation and transformation then aggregated to phlegm. Phlegm obstructing orifices and mind disuse are the core link of AD attack. We found that Yuanzhi Powder within reducing phlegm and opening orifices function can effectively improve the elderly patients with memory impairment symptoms, also can improve memory and cognitive level in AD animal model, and reduced the expression of P-tau protein in hippocampes. Based on it, we put forward the hypothesis: "Yuanzhi powder in the treatment of AD playing a role in the regulation of multiple targetsa through UPS mediated by ubiquitin, may be related to the increasing of the 26S proteasome activity, and inhibition of phosphorylation of tau protein aggregation. This research discusses the mechanism of Yuanzhi Powder in treating AD under the guidance of the theory of traditional Chinese Medicine, around the core theory of "abnormal phosphorylation of tau aggregation" in the pathogenesis of AD, from the perspective of UPS dysfunction and excessive phosphorylation of tau degradation disorder. It takes 26S proteasome as the key point of entry, uses modern molecular biology techniques and methods, and provides objective scientific basis for reducing phlegm and open orifices treatment of AD.