“石菖蒲-远志”药对干预mTOR信号通路防治阿尔兹海默病的作用机制研究

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, which is belongs to dementia category of traditional Chinese medicine(TCM), there is no effective prevention and treatment drug. Mammalian target of rapamycin (mTOR) signaling pathway plays an important role in learning and memory formation and tau protein pathology, to study the pathway is meaning of great significance to find drug targets.. The preliminary study found that Shichangpu-Polygalaceae is the highest frequency of drugs on the TCM treatment of senile dementia recipes. The experiments confirmed that both of them can improve the learning and memory but the mechanism of action is unclear until now. The project aims on the two components of Shichangpu-Polygalaceae, to research some kinds of influences on learning and memory of AD-like dementia, in rats, screening of the drug on the optimal ratio of compatibility, the best concentration and the active time from in vitro and in vivo, the number of dendritic spines, tau protein phosphorylation sites, the change level of pros and pose synapses density protein, neuronal apoptosis and especially from the mTOR two main signal transduction pathways (P13K/Akt, ERK) , in-depth to explore the molecular mechanism for its prevention and treatment of AD. To provide a scientific, objective experimental evidence for clinical safety, effective, reasonable using of these drugs, laid the foundation for exploring the traditional Chinese medicine treatment of AD, but also help to further clarify compound compatibility law.

阿尔兹海默病（AD）是最常见的神经退行性疾病之一，属中医"痴呆"范畴，目前尚无有效的防治药物。哺乳动物雷帕霉素靶蛋白（mTOR）信号通路在学习和记忆的形成、tau蛋白病理中起重要作用，研究该通路对寻找药物靶点具有重要意义。前期研究发现,"石菖蒲-远志"是中医治疗老年性痴呆方剂中出现频次最高的药对。实验证实两药均能增强AD大鼠的学习记忆能力，但深入的作用机制尚不明了。本项目旨在研究"石菖蒲-远志"药对的两种组分对AD样痴呆大鼠学习记忆能力的影响，筛选该药对的最佳配伍比例、浓度和作用时间，从体外和体内两个角度，通过检测树突棘数目、tau蛋白磷酸化位点、突触前后密度蛋白、神经元凋亡尤其从mTOR两条主要信号转导途径(P13K／Akt、ERK )深入探讨其防治AD的分子机制，为临床安全、有效、合理使用该药对提供科学、客观的实验依据，为探索治疗AD的药方奠定基础，也有助于进一步阐明方药配伍规律。

阿尔兹海默病（AD）是最常见的神经退行性疾病之一，属中医“痴呆”范畴，目前尚无有效的防治药物。哺乳动物雷帕霉素靶蛋白（mTOR）信号通路在学习和记忆的形成、tau蛋白病理中起重要作用，研究该通路对寻找药物靶点具有重要意义。前期研究发现,“石菖蒲-远志”是中医治疗老年性痴呆方剂中出现频次最高的药对。实验证实两药均能增强AD大鼠的学习记忆能力，但深入的作用机制尚不明了。本项目研究了“石菖蒲-远志”药对的两种组分对AD样痴呆大鼠学习记忆能力的影响，筛选该药对的最佳配伍比例、浓度和作用时间，从体外和体内两个角度，通过检测树突棘数目、tau蛋白磷酸化位点、突触前后密度蛋白、神经元凋亡尤其从mTOR两条主要信号转导途径(P13K／Akt、ERK )深入探讨其防治AD的分子机制，为临床安全、有效、合理使用该药对提供科学、客观的实验依据，为探索治疗AD的药方奠定基础，也有助于进一步阐明方药配伍规律。