The injured axon: intrinsic mechanisms driving axonal regeneration

Injury to the central nervous system (CNS) often results in permanent neurological impairments because axons fail to regenerate and re-establish lost synaptic contacts. By contrast, peripheral neurons can activate a pro-regenerative program and regenerate following a nerve lesion. This relies on an intricate intracellular communication system between the severed axon and the cell body. Locally activated signaling molecules are retrogradely transported to the soma to promote the epigenetic and transcriptional changes required for the injured neuron to regain growth competence. These signaling events rely heavily on intra-axonal translation and mitochondrial trafficking into the severed axon. Here, we discuss the interplay between these mechanisms and the main intrinsic barriers to axonal regeneration. We also examine the potential of manipulating these processes for driving CNS repair.