Advances in the Signaling Pathways Downstream of Glial-Scar Axon Growth Inhibitors

Glial scars, which form after CNS injuries, inhibit axon regeneration by upregulating molecules like chondroitin sulfate proteoglycans (CSPGs). These molecules create a non-permissive environment that hinders the regrowth of injured axons, contributing to functional loss. CSPGs bind to transmembrane receptors, such as PTPσ and LAR, triggering intracellular signaling pathways that suppress axon elongation. Understanding these pathways is crucial for developing therapies to promote axon regeneration after CNS injuries. The review explores recent advancements in identifying CSPG signaling pathways and their potential as molecular targets for treating CNS injuries, primarily focusing on mammalian models while also considering relevant findings in non-mammalian species like lampreys.

• 1
  PTPσ and LAR, two members of the LAR subfamily of receptor protein tyrosine phosphatases, bind CSPGs with high affinity and mediate suppression of axon elongation by CSPGs.
• 2
  Multiple intracellular signals, including RhoA, Akt, GSK-3β, and Erk, mediate CSPG inhibition on neuronal growth. These signals converge with those of myelin-derived growth inhibitors and repulsive guidance molecules.
• 3
  PTPσ and LAR utilize both convergent (RhoA, Akt, Erk, MAP1B) and divergent (CRMP2, APC, S6 kinase, CREB for PTPσ; cofilin, PKCζ, LKB1 for LAR) signaling pathways to convey CSPG inhibition in neurons.