Wang Chong, Yu Jin-Tai, Miao Dan, Wu Zhong-Chen, Tan Meng-Shan, Tan Lan
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Mol Neurobiol. 2014 Feb;49(1):120-35. doi: 10.1007/s12035-013-8505-8. Epub 2013 Jul 14.
The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that can sense environmental stimuli such as growth factors, energy state, and nutrients. It is essential for cell growth, proliferation, and metabolism, but dysregulation of mTOR signaling pathway is also associated with a number of human diseases. Encouraging data from experiments have provided sufficient evidence for the relationship between the mTOR signaling pathway and Alzheimer's disease (AD). Upregulation of mTOR signaling pathway is thought to play an important role in major pathological processes of AD. The mTOR inhibitors such as rapamycin have been proven to ameliorate the AD-like pathology and cognitive deficits effectively in a broad range of animal models. Application of mTOR inhibitors indicates the potential value of reducing mTOR activity as an innovative therapeutic strategy for AD. In this review, we will focus on the recent process in understanding mTOR signaling pathway and the vital involvement of this signaling pathway in the pathology of AD, and discuss the application of mTOR inhibitors as potential therapeutic agents for the treatment of AD.
雷帕霉素的哺乳动物靶点（mTOR）是一种高度保守的丝氨酸/苏氨酸激酶，它能够感知诸如生长因子、能量状态和营养物质等环境刺激。它对于细胞生长、增殖和代谢至关重要，但mTOR信号通路的失调也与许多人类疾病相关。来自实验的令人鼓舞的数据为mTOR信号通路与阿尔茨海默病（AD）之间的关系提供了充分证据。mTOR信号通路的上调被认为在AD的主要病理过程中起重要作用。雷帕霉素等mTOR抑制剂已被证明能在多种动物模型中有效改善类AD病理和认知缺陷。mTOR抑制剂的应用表明降低mTOR活性作为AD的一种创新治疗策略具有潜在价值。在本综述中，我们将聚焦于理解mTOR信号通路的最新进展以及该信号通路在AD病理中的重要参与，并讨论mTOR抑制剂作为AD潜在治疗药物的应用。
