Inhibition of Chondroitin Sulfate Proteoglycans by APRIL.

Chondroitin sulfate proteoglycans (CSPGs) are major constituents of the extracellular matrix and well-established obstacles to regeneration in the central nervous system. As such, they are promising targets for therapy in neurological pathologies where repair is needed, such as spinal cord injuries, and multiple sclerosis. Since CSPGs mediate their inhibitory functions by interacting with signaling protein partners through their variably sulfated chondroitin sulfate glycosaminoglycan (CS-GAG) chains, blocking these epitopes presents a path to promoting repair. A member of the tumor necrosis factor (TNF) superfamily, a proliferation-inducing ligand (APRIL) has been shown to bind to CSPGs. Here we describe in vitro methods to evaluate APRIL's ability to block CSPGs from interacting with their partner proteins and promote neuronal growth.