Sulfated glycans in network rewiring and plasticity after neuronal injuries

Biopolymers in the human body belong to three major classes: polynucleotides (DNA, RNA), polypeptides (proteins) and polysaccharides (glycans). Although striking progress in our understanding of neurobiology has been achieved through a focus on polypeptides as the main players, important biological functions are also expected to be attributable to glycans. Nonetheless, the significance of glycans remains largely unexplored. In this review, we focus on the roles of sulfated glycans. Axonal regeneration/sprouting after injuries does not easily occur in the adult mammalian central nervous system. This is due to the low intrinsic potential of regeneration and the emerging inhibitory molecules. The latter include the sulfated long glycans chondroitin sulfate (CS) and keratan sulfate (KS). Enzymatic ablation of CS or KS, and genetic ablation of KS promote functional recovery after spinal cord injury. Interestingly, the combination of CS and KS ablations exhibits neither additive nor synergistic effects. Thus, KS and CS work in the same pathway in inhibition of axonal regeneration/sprouting. Furthermore, CS has been implicated in neural plasticity as a functional component of the perineuronal nets surrounding inhibitory interneurons. Elucidation of the mechanisms of action for KS and CS will pave the way to treatments to promote network rewiring and plasticity after neuronal injuries.