Chondroitin sulphate proteoglycans in the central nervous system: changes and synthesis after injury

Abstract

Chondroitin sulphate proteoglycans (CSPGs) are up-regulated in the central nervous system after injury, specifically around the lesion site where the glial scar forms. This structure contains astrocytes, oligodendrocyte precursor cells, microglia and meningeal cells, and forms an inhibitory substrate for axon re-growth. CSPGs have been shown to be closely involved in this neuronal growth inhibition, specifically through their sugar chains. These chains are composed of repeats of the same disaccharide unit carrying sulphate groups in different positions. The sulphation pattern directly influences the CSPG binding properties and function; the specific sulphation pattern required for the inhibitory activity of these molecules on axon growth is unknown at present. The expression of the chondroitin sulphotransferases, which sulphate the disaccharide residues of CSPGs and thus are responsible for the structural diversity of the chondroitin sulphate sugar chains, is regulated differently in central nervous system during development and after injury, suggesting the implication of a specific sulphation pattern in the inhibitory activity of CSPGs.

Dexamethasone-coated neural probes elicit attenuated inflammatory response and neuronal loss compared to uncoated neural probes

“…Upregulated CSPGs have differential sulfation patterns (Properzi et al, 2003;Properzi and Fawcett, 2005) which differentially inhibit neurite outgrowth (Gilbert et al, 2005). Following chondroitinase treatment, glycosaminoglycan removal enhances neurite outgrowth, suggesting an inhibitory role for CSPGs (Bradbury et al, 2002).…”

Biomaterials for the central nervous system

“…A possible contributing factor to the loss of signal is the formation of glial scar around the electrodes, which is part of the inflammatory reaction to a foreign body in the CNS. The glial scar acts as a barrier that inhibits axon re-growth and may possibly interfere with signalling by insulating electrodes from nearby neurons (Turner et al 1999;Cui et al 2003;Properzi et al 2003;Biran et al 2005). Alternately, the glial scar could be representative of a general inflammatory response that compromises the functional state of the neuronal circuitry around the electrodes.…”

Discrimination of GalNAc (4S/6S) sulfation sites in chondroitin sulfate disaccharides by chip-based nanoelectrospray multistage mass spectrometry

“…A chondroitin chain can exhibit over 100 disaccharide units; each of these dissacharides can be unsulfated or sulfated in variable positions and quantities by chondroitin sulfotransferase enzymes [8]. CS heterodimers may be sulfated to hydroxyl groups on C4 of GalNAc, known as CS-A (Fig.…”