Concept and molecular basis of axonal regeneration after central nervous system injury

Damage to the central nervous system (CNS) leads to the disruption of the axonal network and causes neurological dysfunction. Recovery of neurological functions requires restoration of the axonal network; however, injured axons in the adult mammalian CNS rarely regenerate after injury. Failure of the injured axon to regenerate is attributed at least partly to the inhibitory molecules of the CNS: several proteins have been identified in the CNS that inhibit axonal regeneration. In addition, the molecular mechanisms underlying the manner via which these inhibitors prevent axonal regeneration have been clarified. The neutralization of nonpermissive substrate properties of the CNS has been shown to promote axonal regeneration in an animal model of CNS injury. Drugs that promote axonal regeneration, some of which have undergone clinical trials, have been developed by pharmaceutical companies. However, spontaneous functional recovery occurs sometimes after CNS injury. This review will describe the new concept of the molecular mechanism of restoration of the neuronal network, with a special focus on our recent reports.