目前帕金森病（PD）的治疗没有靶向特效药物，为数不多的已上市药物因为疗效不佳或毒副作用较大难以满足患者需求。申请人在前期工作中发现，维吾尔族药用植物药西瓜的70%乙醇提取物具有显著抗PD作用，随后采用活性示踪分离方法获得了22个葫芦素型三萜类（cucurbitacins）成分，其中化合物KKY-02具有较优的抗PD活性。进一步研究证实KKY-02是通过靶向PD关键靶标HIPK2诱导神经细胞发生保护性自噬；动物实验表明，KKY-02能够显著改善PD模型小鼠的运动功能障碍，具体机制亟待深入研究。本课题拟在前期基础上，深入研究KKY-02对HIPK2的靶向性及其调控的自噬网络，探究该化合物通过靶向HIPK2诱导保护性自噬在体内外PD模型中的分子机制。本课题有望阐明KKY-02为代表的活性成分是否为药西瓜抗PD的物质基础，为药西瓜的开发利用以及新型抗PD民族药物的研发提供科学依据。

Currently, there are no effective targeted drugs for treatment of Parkinson’s disease (PD). Few drugs already on the market are difficult to meet the requirement due to the poor efficacy and side effects. The applicant in the stage of doctoral student's work found that the 70% ethanol extract of Citrullus Colocynthis (L.) Shrad, a characteristic plants in uygur medicine, has a significant anti-PD effect. Subsequently, 22 cucurbitacins components were obtained by the method of active tracing separation, which may be the drug efficacy material base of Citrullus Colocynthis. Further studies found that the compound KKY-02 has a good protective effect on PD. On the basis of this, we found that KKY-02 bind well to the active site of HIPK2, a key target for PD treatment through bioinformatics and system biology methods. Molecular biology experiments showed that KKY-02 might be used to induce cellular protective autophagy to exert a neuroprotective activity by targeting HIPK2. Animal experiments showed that KKY-02 could significantly improve motor dysfunction in MPTP-induced PD model mice, and its specific molecular mechanism needs further study. This topic is intended to further study the compound’s targeting of HIPK2 protein targeting and its regulation of autophagy network, to explore the role of the compound in targeting HIPK2 regulation of autophagy in vitro and in vivo. Taken together, the molecular mechanisms of these compounds will provide new methods and ideas for the precise development of PD therapeutic medicines. Further molecular pharmacology research on these molecules will also provide the foundations for functional study of autophagy in PD.