The role of mTOR signaling pathway in spinal cord injury
The role of mTOR signaling pathway in spinal cord injury
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DOI：
10.4161/cc.21262
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发表时间：
2012-09-01
期刊：
影响因子：
4.3
通讯作者：
Itoi, Eiji
中科院分区：
文献类型：
--
作者：
Kanno, Haruo;Ozawa, Hiroshi;Itoi, Eiji
哺乳动物雷帕霉素靶蛋白（mTOR）信号通路在细胞代谢、增殖和存活等多种细胞功能中发挥重要作用。许多先前的研究表明，mTOR调节中枢神经系统（CNS）创伤和各种疾病中的神经保护和神经再生功能。最近，我们报道了使用雷帕霉素抑制mTOR可以减少小鼠脊髓损伤（SCI）后的神经组织损伤和运动障碍。我们的研究结果表明，在损伤后4小时给予雷帕霉素显著增加了自噬的活性，并减少了损伤脊髓中的神经元损失和细胞死亡。此外，雷帕霉素处理的小鼠在SCI后后肢中显示出比载体处理的小鼠显著更好的运动功能。这些发现表明，在SCI急性期使用雷帕霉素抑制mTOR信号传导产生神经保护作用，并减少损伤部位的继发性损伤。然而，mTOR信号在受损脊髓中的作用尚未完全阐明。在CNS中，各种功能受mTOR信号传导调节，并且SCI后发生多种病理生理过程。在这里，我们讨论了几个悬而未决的问题，并回顾了相关文章的证据，关于mTOR信号通路在SCI后神经保护和神经再生中的作用和机制。
The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in multiple cellular functions, such as cell metabolism, proliferation and survival. Many previous studies have shown that mTOR regulates both neuroprotective and neuroregenerative functions in trauma and various diseases in the central nervous system (CNS). Recently, we reported that inhibition of mTOR using rapamycin reduces neural tissue damage and locomotor impairment after spinal cord injury (SCI) in mice. Our results demonstrated that the administration of rapamycin at four hours after injury significantly increases the activity of autophagy and reduces neuronal loss and cell death in the injured spinal cord. Furthermore, rapamycin-treated mice show significantly better locomotor function in the hindlimbs following SCI than vehicle-treated mice. These findings indicate that the inhibition of mTOR signaling using rapamycin during the acute phase of SCI produces neuroprotective effects and reduces secondary damage at lesion sites. However, the role of mTOR signaling in injured spinal cords has not yet been fully elucidated. Various functions are regulated by mTOR signaling in the CNS, and multiple pathophysiological processes occur following SCI. Here, we discuss several unresolved issues and review the evidence from related articles regarding the role and mechanisms of the mTOR signaling pathway in neuroprotection and neuroregeneration after SCI.