a-突触核蛋白（a-syn）在神经退行性疾病的发病机制中起着重要作用，这些疾病包括帕金森病、路易小体痴呆、阿尔茨海默病、多系统萎缩等，又统称为突触核蛋白病。但目前这些疾病都缺乏有效的治疗药物。我们的前期研究发现何首乌二苯乙烯苷（TSG）能抑制APP转基因AD小鼠海马和大脑皮层a-syn过表达和聚集，抑制老年小鼠纹状体和海马a-syn过表达和聚集。本项目拟应用A53T突变型a-syn转基因小鼠，进一步研究TSG灌胃给药对模型小鼠运动功能的影响，对多个脑区（黑质纹状体、海马、大脑皮层、脑干）和脊髓a-syn 过表达和聚集的影响，在作用机制方面研究TSG对a-syn生成、降解和翻译后修饰的影响，在防治疾病方面研究TSG对a-syn病理学所致的线粒体功能障碍、胶质细胞激活以及由此引起的氧化应激、硝化应激和炎症反应的影响。本项目将为研制防治突触核蛋白病（包括帕金森病痴呆、路易体痴呆）的新药打下基础。

a-Synuclein（a-syn）plays an important role in pathogenesis of multiple neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and multiple system atrophy (MSA), and they are also called synucleinopathies. However, these diseases lack effective drugs in clinic. Our previous studies showed that 2,3,5,4'- Tetrahydroxy-stilbene glucoside (TSG) extracted from Polygonum multiflorum inhibited a-syn overexpression and aggregation in hippocampus and cerebral cortex of APP transgenic mice and in striatum and hippocampus of aged mice. The present project will further investigate the effects of TSG on A53T a-syn transgenic mice, including motor function, and a-syn overexpression and aggregation in multiple brain regions (substantia nigra-striatum, hippocampus, cerebral cortex and brainstem) and spinal cord. For the mechanism study, we will explore the effects of TSG on production, degradation and post-translational modification of a-syn. For the study of prevention and treatment of disease, we will investigate the effects of TSG on a-syn pathology-induced mitochondria dysfunction and glial activation linking oxidative stress, nitrate stress and inflammation. The present project may provide the experimental evidance for developing new drugs to prevent and treat synucleinopathies including parkinson's disease dementia (PDD) and DLB.