The role of mTOR signalling in the axon regeneration

【摘要】：The failure of axon regeneration in the adult mammalian central nervous system(CNS) attributed to two properties of the adult CNS, the inhibitory extrinsic environment and a diminished intrinsic regenerative capacity of mature CNS neurons. Deleting Pten(phosphatase and tensin homolog) in retinal ganglion cells(RGCs) and corticospinal motor neurons(CSMNs) promotes robust axon regeneration. Importantly, the loss of the regrowth potential of axons is accompanied by a corresponding downregulation of m TOR activity in neurons upon completion of development. An injury further diminishes neuronal mTOR activity. Our recent findings suggest that Pten deletion promotes regeneration in a chronic spinal cord injury model, and enhancing neuronal activity by melanopsin/GPCR signaling promotes axon regeneration in adult CNS. We also demonstrated that rapamycin-resistant m TOR function is required for sensory axon regeneration induced by a conditioning lesion. By doing single cell analysis on isolated regenerated neurons, we further revealed the downstream effects underlining m TOR signaling in the axon regeneration.