Mechanisms for modulation of neural plasticity and axon regeneration by chondroitin sulphate

Chondroitin sulphate proteoglycans (CSPGs), consisting of core proteins linked to one or more chondroitin sulphate (CS) chains, are major extracellular matrix (ECM) components of the central nervous system (CNS). Multi-functionality of CSPGs can be explained by the diversity in structure of CS chains that undergo dynamic changes during development and under pathological conditions. CSPGs, together with other ECM components, form mesh-like structures called perineuronal nets around a subset of neurons. Enzymatic digestion or genetic manipulation of CSPGs reactivates neural plasticity in the adult brain and improves regeneration of damaged axons after CNS injury. Recent studies have shown that CSPGs not only act as non-specific physical barriers that prevent rearrangement of synaptic connections but also regulate neural plasticity through specific interaction of CS chains with its binding partners in a manner that depends on the structure of the CS chain.