帕金森病（PD）是临床上最为常见的神经退行性疾病之一，黒质多巴胺能神经元的变性丢失是引发帕金森病的主要病理机制。近年来的研究表明，自噬及凋亡信号通路在多巴胺能神经元变性损伤的过程中发挥着至关重要的作用。现有的研究表明Maged1基因不仅可以通过多种途径介导细胞凋亡，还对细胞的自噬水平也有调节作用。另外有研究报道，PD的致病基因FBXO7可以调节Maged1的功能，影响其下游信号通路。然而Maged1是否参与PD的发生发展过程尚不清楚。本课题拟在原有Maged1研究工作的基础上，1）分析PD发病过程中Maged1表达的变化及可能的被调节机制；2）探讨Maged1调控PD发展的细胞分子机制；3）设计以Maged1为靶点的药物，并观察其在PD治疗过程中的作用。期望通过该项目可以为探索多巴胺能神经元的变性损伤提供新的机制，为临床寻找治疗PD潜在的药物靶点和药物设计提供新的科学支撑。

Parkinson's disease (PD) is a common neurodegenerative disease in the clinic, and degeneration and loss of dopaminergic neurons in substantia nigra is the main pathological features of PD. Many studies have shown that autophagy and apoptosis signaling pathways play an important role in the degenerative damage of dopaminergic neurons. Many studies have shown that Maged1 gene can not only mediate apoptosis through a variety of pathways, but also regulate the level of autophagy of cells. Additionally, a recent study reported that the pathogenic gene FBXO7 of PD can bind to Maged1 and affect its downstream signal. however, the role iof Maged1 in the pathogenesis of Parkinson's disease remains unclear. On the basis of our previous studies on Maged1, 1) To analyze the changes of Maged1 expression and its possible regulatory mechanism in the pathogenesis of PD; 2) To explore the cellular and molecular mechanisms of Maged1 regulating PD; 3) To observe the role of drugs targeting Maged1 in the treatment of PD. This project will further explore a new mechanism for the degenerative damage of dopaminergic neurons and search of the new potential targets and the development of new drug against PD.