Pro-inflammatory roles of chondroitin sulfate proteoglycans in disorders of the central nervous system

Abstract The extracellular matrix of the central nervous system is an interconnected network of proteins and sugars. It is crucial for homeostasis, but its remodeling in neurological diseases impacts both injury and repair. Here we introduce an extracellular matrix family member that participates in immune-matrix interactions, the chondroitin sulfate proteoglycans. Chondroitin sulfate proteoglycans integrate signals from the microenvironment to activate immune cells, and they boost inflammatory responses by binding immunological receptors including toll-like receptors, selectins, CD44, and β1 integrin. Chondroitin sulfate proteoglycans also bind signaling molecules for immune cells such as cytokines and chemokines, and they activate matrix-degrading enzymes. Chondroitin sulfate proteoglycans accumulate in the damaged CNS, including during traumatic brain/spinal cord injury and multiple sclerosis, and they help drive pathogenesis. This Review aims to give new insights into the remodeling of chondroitin sulfate proteoglycans during inflammation, and how these matrix glycoproteins are able to drive neuroinflammation.