帕金森病(PD)是一种多发于中老年人群的中枢神经系统退行性疾病，其主要病理变化是多巴胺(DA)神经元坏死缺失。申请人前期研究发现海带硫酸杂聚糖(UF)对PD小鼠的DA神经元有显著的保护作用，但是其作用机制尚不明确。本项目拟采用细胞模型和动物模型，以PI3K/Akt信号通路逐级信号分子的mRNA转录、蛋白磷酸化和组织病理学变化为指标，深入研究UF是否可以通过PI3K/Akt信号通路的活化抑制DA神经元的凋亡、是否可以通过作用于NGF/TrkA激活PI3K/Akt信号通路，阐明UF通过PI3K/Akt信号通路调节与细胞凋亡密切相关的调控蛋白的表达的作用机制，并针对PI3K/Akt信号通路上下游信号分子和蛋白探寻UF抗PD的作用靶点，以期从细胞、分子及基因水平上探讨UF抑制DA神经元凋亡的分子机制。本研究将解决制约UF药物研发作用机制的瓶颈问题，为UF在PD治疗中的应用提供实验基础和理论依据。

Parkinson's disease (PD) is a progressive neurodegenerative disease with selective loss of dopaminergic neurons in the substantia nigra. Evidence suggests that apoptosis is involoved in the pathogenesis of PD. PI3K/AKT signal channel play an important role in cell apoptosis. Our previous study found the sulfated heteropolysaccharide (UF) had significant protective effect on the DA neuron, Bcl-2 expression increased and Bax expression decreased. However, the molecular mechanisms by which UF protects DA neuron are poorly elucidated. On this basis, in this project we will study the mechanism of UF on PD disease through the PI3K/Akt signal channel both in vitro and vivo. We will study the expression of gene and protein such as Blc-2 family and caspase family in order to confirm PI3K/Akt signal channel had relationship with the protection ability of UF on DA. The UF anti-PD mechanism will be explored on the molecular and genetic level. The results of the research not only supplies new ideas and methods on the anti-PD mechanism study of the sulfated heteropolysaccharide, but also provides the scientific basis for the anti-PD drug development and high-value utilization Saccharina latissima resources.