Scars can serve as double-edged swords in spinal cord injuries—saving a victim's life, but sealing his or her fate as a paraplegic or quadriplegic. The scar forms a wall around the wound, preventing the injury from spreading, but limiting opportunities for neural regeneration. Cells in the scar release molecules that keep severed nerve fibers from passing the damaged tissue, so they cannot connect with their original targets to restore motor and sensory function.Now, a team of researchers from Harvard Medical School and Case Western Reserve University has identified where these potent molecules—called chondroitin sulfate proteoglycans (CSPGs)—bind to the surface of neurons, exposing a novel therapeutic target. Their findings appear online in the journal Science on Oct. 15. "The docking station for these molecules has eluded scientists for nearly two decades," says Harvard Medical School Professor John Flanagan, senior author on the study. "Our collaborator Jerry Silver discovered that CSPGs inhibit regeneration of the central nervous system in the early 1990s, but nobody knew how they were keeping neurons at bay." Now chemists can hunt for small molecules that will block the docking station and explore other approaches to disrupt it. "This discovery suggests that we might be able to treat central nervous system injuries with a pill in the future," says Silver, who is a professor at Case Western Reserve University. "In reality, we'll probably need a drug cocktail because CSPGs are not the only barrier to regeneration." Most scientists had given up on finding a docking station for CSPGs because they suspected such a location did not exist. Like M&Ms, CSPGs are covered in slippery sugar, which coats their sticky interior. The tough sugar coating ruled out the typical interaction with a docking station, or receptor. Flanagan's cell biology lab, however, recently discovered an anomaly—a family of receptors on cells that tolerate and bind to the hard sugar coating itself.
Link