血管紧张素-(1-7)（Ang-(1-7)）是新发现的肾素-血管紧张素系统的重要活性肽，研究表明其对帕金森病（PD）大鼠模型具有神经保护作用，但在PD的α-突触核蛋白（α-syn）病理中的作用尚不明确。预实验发现：hSYNA53T转基因小鼠黑质Ang-(1-7)及Mas受体含量伴随α-syn的病理进程逐步降低；且Ang-(1-7)可调控此模型小鼠黑质多巴胺（DA）能神经元的自噬水平。我们推测：Ang-(1-7)可通过改善DA能神经元的自噬障碍减轻PD的α-syn病理。本项目拟通过黑质区注射Ang-(1-7)，在体探究其对hSYNA53T转基因小鼠行为学特征、α-syn病理及DA能神经元自噬障碍的影响；而后培养黑质原代神经元，离体研究Ang-(1-7)对DA能神经元自噬流的调控及对α-syn清除的影响，从而阐明Ang-(1-7)对PD的α-syn病理的作用和机制，为PD的治疗提供新思路。

Angiotensin-(1-7)(Ang-(1-7)) has been newly identified as an important component of renin-angiotensin system. Several line of evidence suggests that Ang-(1-7) has protective effect on a rat model of Parkinson's disease, but its role in the pathology of α-synuclein(α-syn) in PD remains unclear. Our preliminary study showed that the level of Ang-(1-7) and its Mas receptor in the substantia nigra of hSYNA53T transgenic mice decreased with the pathological progress of α-syn. Besides, we also found that Ang-(1-7) could regulate the autophagic activity of dopaminergic(DA) neurons in hSYNA53T transgenic mice. Based on these findings, we hypothesized that Ang-(1-7) could alleviate the α-syn pathology by ameliorating the dysfunctional autophagy in DA neurons. In this project, we will firstly investigate the effect of Ang-(1-7) on ethology, α-syn pathology and dysfunctional autophagy in DA neurons by injection of Ang-(1-7) to the substantia nigra of hSYNA53T transgenic mice. In addition, we intend to observe the influence of Ang-(1-7) on autophagic flux and clearance of α-syn by culture of primary DA neurons from hSYNA53T transgenic mice. The completion of this project will not only clarify the role of Ang-(1-7) in the pathology of α-syn in PD and the underlying mechanisms, but also provide a new target for the therapies of this devastating disease.