Awakening the stalled axon - Surprises in CSPG gradients

The remarkably poor regeneration of axons seen after injury of the brain and spinal cord can result in permanent loss of neural function. This failure of meaningful regeneration has been attributed to both a low intrinsic growth potential of CNS neurons and extrinsic factors that actively block axon growth in the adult CNS. Injury exacerbates this situation by increasing the expression of and exposure to proteins that actively block axonal growth in the CNS. Much experimental efforts have been aimed at overcoming the extrinsic growth inhibitory environment of the injured brain and spinal cord. A recent publication in Experimental Neurology from Kuboyama and colleagues shows that activation of protein kinase A signaling is responsible for the stalling of axon growth in gradients of CNS inhibitory molecules. This observation is unexpected given the role of cAMP signaling in supporting intrinsic growth mechanisms, emphasizing the need to consider spatial and temporal aspects of intracellular signaling in future strategies for neural repair.