Huang Ziwei, Wang Weihua, Ma Jinjin, Li Bin, Chen Jianquan, Yang Huilin
Department of Orthopaedics, Orthopaedic Institute, The First Affiliated Hospital, Soochow University, Suzhou 215007, China.
Acta Biochim Biophys Sin (Shanghai). 2017 Aug 1;49(8):689-695. doi: 10.1093/abbs/gmx068.
Numerous studies have shown that the intrinsic axonal regenerative capacity of neurons differs between the peripheral and central nervous systems (CNSs). However, the molecular mechanisms controlling intrinsic axonal regenerative capacity are unclear. A better understanding of these mechanisms should aid in the development of effective therapeutic strategies for traumatic nervous system injury, including spinal cord injury. Here, we found that blocking mammalian target of rapamycin (mTOR) activity dramatically diminished axonal regrowth from embryonic cortical neurons. However, mTOR activity was not required for axonal regrowth from adult peripheral sensory neurons. By analyzing the levels of phospho-S6, a downstream target of mTOR, we found that embryonic cortical neurons had a much higher mTOR activity compared with adult peripheral sensory neurons. Our findings suggest that, in the CNS, the mTOR pathway plays a critical role in regulating the regenerative capacity of neurons, in contrast to the peripheral nervous system.
大量研究表明，神经元的轴突内在再生能力在周围神经系统和中枢神经系统（CNS）之间存在差异。然而，控制轴突内在再生能力的分子机制尚不清楚。更好地理解这些机制应有助于开发针对创伤性神经系统损伤（包括脊髓损伤）的有效治疗策略。在此，我们发现阻断雷帕霉素的哺乳动物靶点（mTOR）活性会显著减少胚胎皮质神经元的轴突再生。然而，mTOR活性对于成年周围感觉神经元的轴突再生并非必需。通过分析mTOR的下游靶点磷酸化S6的水平，我们发现与成年周围感觉神经元相比，胚胎皮质神经元具有更高的mTOR活性。我们研究结果表明，与周围神经系统相比，在中枢神经系统中，mTOR信号通路在调节神经元的再生能力中起关键作用。
