Receptors of Chondroitin Sulfate Proteoglycans and CNS Repair

Axon disconnections in the CNS usually cause persistent dysfunction with a very limited recovery and the medical treatments to enhance recovery from neurological deficits due to signal conduction failure are largely restricted. Among numerous factors that contribute to regenerative failure of CNS axons, the extracellular matrix molecules Chondroitin Sulfate Proteoglycans (CSPGs) generated by scar tissues are critical for blocking axon elongation following CNS injuries. Overcoming inhibition by CSPG axon growth inhibitors is very important for promoting successful axon regeneration and functional recovery after CNS injuries. Recent progress in understanding of molecular mechanisms underlying CSPG suppression of neuronal growth may facilitate development of new treatments to surmount scar- mediated inhibition. Particularly, a number of studies demonstrate that CSPG inhibitors convey their suppression of axon growth by interacting with several neuronal transmembrane receptors. Two members of the Leukocyte Common Antigen Related (LAR) phosphatase subfamily, protein tyrosine phosphatase σ and LAR, bind CSPGs with high affinity and mediate CSPG inhibition as functional receptors. CSPGs appear also to bind two receptors for myelin-associated growth inhibitors, Nogo receptors 1 and 3. Transgenic or pharmacological blockade of these receptors significantly surmounts CSPG function and promotes CNS axon regeneration. Identification of the CSPG receptors is likely to facilitate developing novel and selective therapies to promote axon sprouting/regeneration and functional recovery after CNS injuries.