Scar-mediated inhibition and CSPG receptors in the CNS

After a CNS injury, severed axons in adult mammals do not regenerate appreciably due to a reduction in neuron-intrinsic growth capacity and inhibitory extracellular environment. Chondroitin sulfate proteoglycans (CSPGs), generated by scar tissues, contribute to this limiting environment. The main in vivo approach to overcoming inhibition by CSPGs is enzymatic digestion with chondroitinase ABC (ChABC). Recent studies indicate that protein tyrosine phosphatase σ (PTPσ) and LAR, are functional receptors that bind CSPGs with high affinity and mediate CSPG inhibitory effects. CSPGs also may act by binding to two receptors for myelin-associated growth inhibitors, Nogo receptors 1 and 3 (NgR1 and NgR3), suggesting that CSPGs have multiple mechanisms by which they inhibit axon growth.

• 1
  Two members of the LAR phosphatase subfamily, PTPσ and LAR, are functional receptors that bind CSPGs with high affinity and mediate CSPG inhibitory effects.
• 2
  CSPGs may also inhibit axon growth by binding to Nogo receptors 1 and 3 (NgR1 and NgR3), which are receptors for myelin-associated growth inhibitors.
• 3
  The inhibitory actions of CSPGs are dependent on the sulfation pattern of GAG chains, as preventing GAG sulfation eliminates much of the inhibitory activity on axon growth in vitro.