Downstream effector molecules in successful peripheral nerve regeneration

The robust axon regeneration that occurs following peripheral nerve injury is driven by transcriptional activation of the regeneration program and by the expression of a wide range of downstream effector molecules from neuropeptides and neurotrophic factors to adhesion molecules and cytoskeletal adaptor proteins. These regeneration-associated effector molecules regulate the actin-tubulin machinery of growth-cones, integrate intracellular signalling and stimulatory and inhibitory signals from the local environment and translate them into axon elongation. In addition to the neuronally derived molecules, an important transcriptional component is found in locally activated Schwann cells and macrophages, which release a number of cytokines, growth factors and neurotrophins that support neuronal survival and axonal regeneration and that might provide directional guidance cues towards appropriate peripheral targets. This review aims to provide a comprehensive up-to-date account of the transcriptional regulation and functional role of these effector molecules and of the information that they can give us with regard to the organisation of the regeneration program.