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The role of mTOR signaling pathway in spinal cord injury
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Pages 3175 - 3179
http://dx.doi.org/10.4161/cc.21262
Keywords: apoptosis, autophagy, mTOR, rapamycin, spinal cord injury
Authors: Haruo Kanno, Hiroshi Ozawa, Akira Sekiguchi, Seiji Yamaya, Satoshi Tateda, Kenichiro Yahata and Eiji Itoi
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Abstract:
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.
Received: May 30, 2012; Accepted: June 25, 2012; Published Online: August 16, 2012
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