神经退行性疾病是体内淀粉样蛋白异常自组装聚集沉积引发的疾病，其中帕金森病(Parkinson disease，PD)为最常见疾病之一，但迄今仍无理想防治方法。异常自组装聚集的alpha-突触核蛋白(alpha-synuclein，AS)是帕金森病患者脑内特征性物质的主要成份，是引起临床症状发生、发展及受累脑区变性的重要原因。研究表明，金属离子能驱动AS蛋白异常聚集，引发疾病，而一些天然化合物，如姜黄素，儿茶素及海藻糖长期用于中医临床治疗。本项目拟从AS蛋白入手，研究金属离子驱动蛋白异常自组装聚集沉淀的分子机制，以及促进该蛋白在细胞中的过表达、异常自组装聚集及引发神经毒性的作用通路，并进一步研究上述化合物对这些过程的干预，并通过PD模型动物考察对大鼠记忆和运动行为的改善，以期实现对蛋白质组装体结构控制，清除蛋白异常自组装聚集体，减少由此引发的神经毒性，为此类疾病的防治及新药开发提供理论基础。

Neurodegenerative diseases involve the abnormal self-assembly and aggregation of amyloid proteins. Parkinson's disease (PD) is one of the most common neurodegenerative diseases, and has not been efficiently prevented and cured to date. alpha-synuclein (AS) of abnormal self-assembly and aggregation is a major component in Lewy bodies which is the pathological hallmark in the brain tissues of PD patients, being important resource leading to the clinical symptoms. It is reported that metal ions are capable of triggering the abnormal self-assembly of amyloid protein and causing the diseases, whilst some natural compounds, such as curcumin, catechin and trehalose, have been used in traditional Chinese medicine for the treatment of such diseases for a long time. This program will focus on AS protein to reveal the molecular mechanism of metal ions affecting on the abnormal self-assembly, overexpression and neurotoxicity of AS in cell system. Furthermore, the natural compounds will be used to interfere with the metal ion-induced abnormal processes and improve the memory and action behavior of PD mouse models. The program is attempted to control the self-assembly of AS, remove the abnormal aggregates, attenuate the neurotoxicity induced by the aggregates, and provide theoretical basis for the prevention and treatment of neurodegenerative diseases and development of new drugs.