Spinal cord injury disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. The most important reason for such permanent functional deficits is the failure of injured axons to regenerate after injury. In principle, the functional recovery could be achieved by two forms of axonal regrowth: the regeneration of lesioned axons which will reconnect with their original targets and the sprouting of spared axons that form new circuits and compensate for the lost function. Our recent studies reveal the activity of the mammalian target of rapamycin (mTOR) pathway, a major regulator of new protein synthesis, as a critical determinant of axon regrowth in the adult retinal ganglion neurons. This proposed study will focus on examining the possibility of whether manipulating the mTOR activity could promote the regrowth of descending corticospinal axons and restoration of lost functions after spinal cord injury. We expect that these experiments will provide important insights into the therapeutic potential of manipulating mTOR pathway in promoting axon regrowth and functional recovery after spinal cord injury.
Spinal cord injury disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. This is largely due to the fact that injured axons cannot regenerate. However, currently there is no treatment to promote axon regeneration. Our recent studies in optic nerve injury models discovered that the mTOR pathway is critical in determining the axonal regenerative ability. This application is designed to explore the involvement of this pathway in axon regeneration and compensatory sprouting after spinal cord injury. In addition to genetic studies, we also propose to test the effects of pharmacological means of modulating mTOR activation on axon regeneration and functional recovery after injury. We expect that these studies will provide important insights into designing therapeutics for spinal cord injury and other types of CNS injury.
| Liu, Kai; Lu, Yi; Lee, Jae K et al. (2010) PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 13:1075-81 |
| Sun, Fang; He, Zhigang (2010) Neuronal intrinsic barriers for axon regeneration in the adult CNS. Curr Opin Neurobiol 20:510-8 |
