帕金森病(PD)是目前最常见的神经退行性疾病之一，但发病机制不明，缺乏有效治疗手段。我们前期实验研究发现中药单体马钱苷可以挽救MPTP诱导的小鼠脑内多巴胺丢失，可以抑制与自噬相关的mTOR上游分子AKT表达，以及抑制自噬蛋白LC3-II的表达。这些结果提示马钱苷有可能通过自噬发挥作用发挥其神经保护功能。本项目将采用神经毒素MPTP建立PC12细胞实验模型，并给予马钱苷给药，并加入mTOR抑制剂和诱导剂作为对比，检测细胞形态多个指标观察马钱苷对于PD小鼠的神经保护作用，结合细胞形态学观察，检测氧化应激和与自噬密切相关的蛋白研究来验证马钱苷是否通过影响mTOR自噬机制实现其神经保护效应的假设。该项目的实施将为马钱苷治疗PD提供强有力的临床前研究，具有很好的应用前景。

Parkinson’s disease(PD) is one of the most frequently neurodegenerative diseases，while there is no effective therapy and the pathogenesis is still unknown. Our previous study showed that Chinese medicine-loganin is able to not only rescue MPTP-induced DA loss in Parkinsonian mice, but also can the expression of AKT, which is upstream molecule of mTOR, Loganin can inhibit the expression of LC3-II as well. These data suggest that loganin possess neuroprotective effects and possibly via the mTOR-autophagy pathway. In this project, MPTP-induced cell models will be established then with loganin treatment. m-TOR promoter and inhibitor are also applied in parallel with evaluation of loganin treatment. Cell morphology and attachment on plate will be detected to observe the neuroprotective effects of loganin. Furthermore, we will study multiple pathogenesis of PD, such as oxidative stress, autophagy related signals to figure out how mTOR-autophagy pathway to realize the PD progression. This project will provide important data for loganin application in PD treatment.

帕金森病（PD）是目前最常见的神经退行性疾病之一，但发病机制不明，缺乏有效治疗手段。马钱（子）苷（Loganin，LOG）是一种中药天然单体，可调节大鼠的机体免疫反应、减轻氧化应激损伤；并具有神经营养作用。本项目即利用神经毒素MPTP处理的小鼠、斑马鱼、细胞作为帕金森病模型，通过设置马钱苷预防给药组（MPTP诱导PD前给药）和治疗给药组（MPTP诱导PD后给药）探讨了LOG对PD的预防和治疗效果、及其作用机制。研究发现：与对照组相比，LOG治疗给药可抑制MPTP诱导的PD小鼠纹状体内多巴胺和TH表达的下降和多巴胺能神经元的丢失，并能挽救MPTP诱导PD小鼠的运动障碍，但LOG预防给药上述各指标未见差异；LOG治疗还可以挽救MPTP所致的斑马鱼畸形、及多巴胺神经元丢失和运动障碍；本项目还揭示了LOG可能通过凋亡、炎症反应、细胞自噬等途径实现神经保护；体外细胞实验明确了LOG通过抑制PI3K/Akt/mTOR和JNK 信号通路的作用机制。本项目在2017共发表SCI 论文3篇，培养研究生2名；该项目的实施为马钱苷治疗PD提供了强有力的临床前研究基础，具有很好的应用前景。