Targeting Intracellular Signaling Molecules Within the Neuron to Promote Repair After Spinal Cord Injury

Axonal elongation, pathfinding, branching, and the formation of synaptic contacts are highly complex processes that involve the coordination of various environmental cues such as cell adhesion molecules, gradients of trophic molecules, and the extracellular matrix. The constant exposure of this diverse array of environmental cues in the developing or injured central nervous system to the highly motile tip of the growing axon, the growth cone, is integrated by intracellular signaling cascades that initiate dynamic cytoskeletal remodeling and altered gene expression. This results in either axonal growth or retraction, growth cone collapse, fasciculation, or synapse formation and stabilization. It has been recently demonstrated that direct modulation of several intracellular signaling pathways in vitro and in vivo can override environmental cues and direct axonal growth responses. The current review will examine intracellular signaling pathways in the neuron putatively involved in axon growth, will examine how these cascades can be modulated, and will discuss the implications of these findings for spinal cord injury repair.