Lipton Jonathan O, Sahin Mustafa
F.M. Kirby Center for Neurobiology, Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
F.M. Kirby Center for Neurobiology, Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA.
Neuron. 2014 Oct 22;84(2):275-91. doi: 10.1016/j.neuron.2014.09.034.
The mechanistic target of rapamycin (mTOR) signaling pathway is a crucial cellular signaling hub that, like the nervous system itself, integrates internal and external cues to elicit critical outputs including growth control, protein synthesis, gene expression, and metabolic balance. The importance of mTOR signaling to brain function is underscored by the myriad disorders in which mTOR pathway dysfunction is implicated, such as autism, epilepsy, and neurodegenerative disorders. Pharmacological manipulation of mTOR signaling holds therapeutic promise and has entered clinical trials for several disorders. Here, we review the functions of mTOR signaling in the normal and pathological brain, highlighting ongoing efforts to translate our understanding of cellular physiology into direct medical benefit for neurological disorders.
雷帕霉素的作用靶点(mTOR)信号通路是一个关键的细胞信号枢纽,它与神经系统本身一样,整合内部和外部信号,以引发包括生长控制、蛋白质合成、基因表达和代谢平衡在内的关键输出。mTOR信号通路对脑功能的重要性体现在众多与之功能失调相关的疾病中,如自闭症、癫痫和神经退行性疾病。对mTOR信号通路进行药理学调控具有治疗前景,并且已经针对多种疾病进入了临床试验阶段。在此,我们综述了mTOR信号通路在正常和病理状态下大脑中的功能,重点介绍了为将我们对细胞生理学的理解转化为对神经系统疾病的直接医学益处而正在进行的努力。