Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, Via Pansini, 5, 80131 Naples, Italy.
Curr Opin Pharmacol. 2011 Aug;11(4):378-94. doi: 10.1016/j.coph.2011.05.003. Epub 2011 Jun 7.
The acronym mTOR defines a family of serine-threonine protein kinase called mammalian target of rapamycin. The major role of these kinases in the cell is to merge extracellular instructions with information about cellular metabolic resources and to control the rate of anabolic and catabolic processes accordingly. In mammalian cells mTOR is present in two distinct heteromeric protein complexes commonly referred to as mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), involved in the control of a wide variety of cellular processes. It has been recently reported that compounds acting modulating mTOR activity, beside mediating the well recognized processes exploited in the anticancer and immunosuppressant effects, are provided with neuroprotective properties. In fact, mTOR is involved in the mechanism of PI3K/Akt-induced upregulation of glutamate transporter 1, GLT1, that is linked to several neuronal disorders such as stroke, Alzheimer's disease, and amyotrophic lateral sclerosis. Furthermore, in adult brain mTOR is crucial for numerous physiological processes such as synaptic plasticity, learning, memory, and brain control of food uptake. Moreover, the activation of mTOR pathway is involved in neuronal development, dendrite development and spine morphogenesis.
mTOR 是丝氨酸/苏氨酸蛋白激酶家族的缩写，称为哺乳动物雷帕霉素靶蛋白。这些激酶在细胞中的主要作用是将细胞外的指令与细胞代谢资源的信息融合在一起，并相应地控制合成代谢和分解代谢过程的速度。在哺乳动物细胞中，mTOR 存在于两种不同的异源二聚体蛋白复合物中，通常称为 mTOR 复合物 1（mTORC1）和 mTOR 复合物 2（mTORC2），参与控制多种细胞过程。最近有报道称，调节 mTOR 活性的化合物除了介导在抗癌和免疫抑制作用中被广泛利用的过程外，还具有神经保护特性。事实上，mTOR 参与了 PI3K/Akt 诱导的谷氨酸转运体 1（GLT1）上调的机制，GLT1 与多种神经元疾病有关，如中风、阿尔茨海默病和肌萎缩侧索硬化症。此外，在成年大脑中，mTOR 对于许多生理过程至关重要，如突触可塑性、学习、记忆和大脑对食物摄入的控制。此外，mTOR 通路的激活参与神经元发育、树突发育和脊柱形态发生。
