中文摘要：

哺乳动物雷帕霉素靶蛋白mTOR是一个进化上十分保守的蛋白激酶,属于PIKK超家族。在细胞内mTOR存在两种功能不同的复合体mTORC1和mTORC2。mTOR主要通过接受上游信号分子Rheb、TSC1/TSC2的调控来整合细胞内外信号,其下游效应器是4E-BP和p70S6K,通过影响特定mRNA的翻译调节细胞的生长和增殖。在神经系统方面,神经元的发育、突触可塑性的调节、学习和记忆的形成都依赖于适当的mTOR通路的活化。新近的研究显示,神经退行性疾病阿尔茨海默病患者表现mTOR通路的异常,在双转基因鼠中,APP和PS1表达与mTOR/P70S6K下调关联,并影响精神状态评分。mTOR信号通路生理功能和调节机制的研究对了解AD的发病机理和寻找药物靶点具有重要意义。

英文摘要：

Mammalian target of rapamycin（mTOR） is an evolutionarily conserved protein kinase and belongs to the phosphoinositide-3-kinase-related kinase family.In mammalian cells,two structurally and functionally distinct mTOR complexes have been identified： mTORC1 and mTORC2.The major role of this kinase is to integrate intracellular and extracellular signals by upstream regulators Rheb and TSC1/TSC2,and then acting on the downstream effectors 4EBP and p70S6K,regulate cell growth and proliferation by influencing the translation of specific mRNA.In the nervous system,neural development,synaptic plasticity,and memory formation require proper mTOR activity.Recent studies showed that abnormalities of mTOR signaling pathway is implicated in Alzheimer＇s disease.In double transgenic mouse,expression of APP and PS1 relates with down-regulation of mTOR/P70S6K,and influences mental status score.Studies on physiological function and the regulation mechanisms of mTOR signaling may promote a better understanding of the disease pathogenesis and development of more effective drug targets for Alzheimer＇s disease treatment.