Overcoming Chondroitin Sulphate Proteoglycan Inhibition of Axon Growth in the Injured Brain: Lessons from Chondroitinase ABC

The presence of numerous axon-inhibitory molecules limits the capacity of injured neurons in the adult mammalian central nervous system (CNS) to regenerate damaged axons. Among others, chondroitin sulphate proteoglycans (CSPGs) enriched in glycosaminoglycan (GAG) chains, acting intracellularly via Rho GTPase activation and cytoskeletal modification, prevent axon re-growth after injury. However, axon regeneration can be induced by modulating the extrinsic environment or the intrinsic neural response to axon extension. Among other strategies, the use of chondroitinase ABC (ChABC) to degrade GAGs and decrease CSPG-associated inhibition has been analyzed. Recent reports have extended the use of this enzyme, in combination with cell transplantation or pharmacological treatment. The steady advances made in these combinations offer promising perspectives for the development of new therapies to repair the injured nervous system.