Rho signaling and axon regeneration

Several major advances in our understanding of axon regeneration and functional repair in the central nervous system (CNS) together with new insights about molecular signaling pathways have led to development of viable drug candidates to treat spinal cord injury. In this review, we focus on Rho, an intracellular small GTPase that is part of a family of highly related proteins that are present in all cells as important signaling switches. Multiple lines of evidence have validated the Rho pathway as important in controlling axon growth and regeneration after neurotrauma in the CNS. The first part of this review will provide the evidence that Rho is a convergent point of signaling important for axon regeneration in the growth inhibitory environment of the adult CNS. The second part of the review will focus on efforts to target Rho to promote regeneration in vivo. The final section of the review will summarize clinical results with Cethrin, a Rho inhibitor that has completed phase I/IIa clinical testing.