Department of Neurology, PENN Epilepsy Center, University of Pennsylvania, 3 West Gates Bldg, 3400 Spruce St, Philadelphia, PA 19104, USA.
Trends Mol Med. 2011 Dec;17(12):734-42. doi: 10.1016/j.molmed.2011.07.008. Epub 2011 Sep 2.
The mTOR signaling network functions as a pivotal regulatory cascade during the development of the cerebral cortex. Aberrant hyperactivation of mTOR as a consequence of loss-of-function gene mutations encoding mTOR inhibitor proteins such as TSC1, TSC2, PTEN and STRADα has been recently linked to developmental cortical malformations associated with epilepsy and neurobehavioral disabilities. Investigation of mTOR signaling in these disorders provides for the first time exciting future avenues for assessment of biomarkers, patient stratification and prognostic measures as well as the opportunity for targeted therapy to regulate mTOR activity across all age groups. As we learn more about mTOR and its activity in the developing brain, many challenges will arise that must be overcome before widespread clinical therapeutics can be implemented.
mTOR 信号网络在大脑皮层发育过程中作为一个关键的调节级联发挥作用。最近发现，由于编码 mTOR 抑制剂蛋白（如 TSC1、TSC2、PTEN 和 STRADα）的功能丧失基因突变导致 mTOR 异常过度激活，与癫痫和神经行为障碍相关的发育性皮质畸形有关。对这些疾病中的 mTOR 信号的研究首次为评估生物标志物、患者分层和预后措施以及靶向治疗以调节所有年龄段的 mTOR 活性提供了令人兴奋的未来途径。随着我们对 mTOR 及其在发育中的大脑中的活性的了解越来越多，在广泛实施临床治疗之前，还会出现许多必须克服的挑战。
