Chondroitin sulfate proteoglycan (CSPG) (CSPG)

Chondroitin sulfate proteoglycans (CSPGs) are a major class of extracellular matrix (ECM) molecules that become highly upregulated following central nervous system (CNS) injury, forming a dense inhibitory environment known as the glial scar (Silver & Miller, 2004). These molecules consist of a core protein with covalently attached glycosaminoglycan (GAG) side chains, which are primarily responsible for their potent inhibition of axonal regeneration and plasticity (Dyck & Karimi-Abdolrezaee, 2015). In the healthy brain, CSPGs contribute to structural integrity and the formation of perineuronal nets, but after trauma, they act as physical and chemical barriers to repair. Therapeutic strategies targeting CSPGs include enzymatic digestion of the inhibitory GAG chains using Chondroitinase ABC or blocking the interaction between CSPGs and their neuronal receptors, such as Protein Tyrosine Phosphatase sigma (PTPσ) (Lang et al., 2015). By neutralizing the inhibitory properties of the glial scar, these interventions aim to promote functional recovery in conditions like spinal cord injury and stroke. Current research is focused on improving the delivery of these agents and managing the potential for maladaptive plasticity, such as neuropathic pain (Bradbury & Burnside, 2019).

Other names

CSPGsLecticansGlial scar ECMChondroitin sulfate glycosaminoglycansCS-GAGsPerineuronal net components

Therapeutic strategies primarily involve the enzymatic digestion of the inhibitory chondroitin sulfate (CS) glycosaminoglycan (GAG) chains using Chondroitinase ABC, or the pharmacological blockade of CSPG receptors such as Protein Tyrosine Phosphatase sigma (PTPσ) and Leukocyte Common Antigen-Related (LAR) phosphatase to prevent the activation of RhoA-mediated growth cone collapse (Bradbury & Burnside, 2019; Lang et al., 2015).