Signaling pathways that regulate axon regeneration

Neurons in the mammalian central nervous system (CNS) cannot regenerate axons after injury. in contrast, neurons in the mammalian peripheral nervous system and in some non-mammalian models, such as C. elegans and Drosophila, are able to regrow axons. Understanding the molecular mechanisms by which these neurons support axon regeneration will help us find ways to enhance mammalian CNS axon regeneration. Here, recent studies in which signaling pathways regulating naturally-occurring axon regeneration that have been identified are reviewed, focusing on how these pathways control gene expression and growth-cone function during axon regeneration.

• 1
  A large-scale RNAi-based genetic screen has identified dual leucine zipper-bearing kinase 1 (DLK-1) as a key regulator of axon regeneration
• 2
  Genetic interaction experiments have identified MKK-4 (MAP kinase kinase 4, MAP2K4) and PMK-3 (p38 MAP kinase) as downstream mediators of DLK-1 to control axon regeneration.
• 3
  peripheral axotomy-induced regenerative axon growth is mediated by the inactivation of glycogen synthase 3 (GSK3), which in turn controls growth-cone microtubule assembly via the microtubule-binding protein adenomatous polyposis coli (APC) and CLiP-associating proteins (CLASPs)