帕金森病(PD)发生的病理学特征是黑质多巴胺能神经元内形成路易小体，其主要成分是错误折叠的α-突触核蛋白（α-syn），通过病理性聚合蛋白的自蔓延传染促进病情的进展。前期研究发现熟地平颤方可以通过下调过度激活的MAPK/ERK通路减轻过表达α-syn诱导的细胞损伤，拮抗长期左旋多巴治疗促进α-syn异常聚集的过程。本课题在前期研究的基础上进一步研究α-syn异常聚集的关键机制，提出如下假说：PLK2，CK2，PP2A 蛋白激酶的活性改变会直接影响α-syn C端Ser129的磷酸化，激活Calpain-1对α-syn C端的异常剪切，造成α-syn错误折叠和异常聚集，促进异常蛋白在细胞间发生转移和神经系统内播散，导致PD病情加重。同时明确熟地平颤方在维持α-syn的正常构象，防止其发生错误折叠和异常聚集的具体作用靶点，深入探寻熟地平颤方在延缓PD病情进展中的机制。

The main pathological feature of Parkinson's disease (PD) is the formation of Lewy bodies in dopaminergic neurons in the substantia nigra. Lewy bodies are composed primarily of misfolded α-synuclein. And self-propagating and infection of pathological aggregate proteins promote disease progression. Our previous studies had found that Shudipingchan Prescription can reduce α-synuclein (α-syn) overexpression induced cell damage by down-regulating excessive activation of MAPK/ERK pathway and antagonise α-syn aggregation process which is accelerated by Long-term L-dopa treatment. This study focuses on the key mechanism of α-syn aggregation on the basis of the previous researches. Our purpose is to verify the direct influence of PLK2, CK2 and PP2A activity change on the Ser129 phosphorylation of c-terminal of α-syn and activation of Calpain-1 for α-syn the abnormal shear on c-terminal, which causes misfolding and aggregation of α-syn and promotes the transfer of abnormal proteins between cells and dissemination in nervous system, and finally leads to the aggravation of PD. And we will also define the specific target of Shudipingchan Prescription on preventing α-syn misfolding and aggregation and maintain the normal conformation of α-syn, and explore the mechanism of Shudipingchan Prescription in delaying the progression of PD.