Scars are a mixed blessing in spinal cord injuries—saving a victim’s life, but sealing his fate as a paraplegic. 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 growing past the damaged tissue, so they cannot reconnect to restore motor and sensory function.
Now, a team of researchers from HMS and Case Western Reserve University has identified where these potent molecules—called chondroitin sulfate proteoglycans (CSPGs)—bind to the surface of neurons, revealing a novel therapeutic target. Their findings appeared online Oct. 15 in Science.
Most researchers 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. John Flanagan, an HMS professor of cell biology, and colleagues, however, recently discovered an anomaly—a family of receptors on cells that tolerate and bind to the hard sugar coating itself.
Flanagan wondered if one of these receptors might recognize CSPGs. Motivated by the therapeutic potential of such a discovery, Flanagan lab research fellow Yingjie Shen and graduate student Alan Tenney—first authors on the study—conducted initial experiments in test tubes and showed that CSPGs did, indeed, bind to one of these receptors. Careful follow-up experiments in culture dishes on neurons missing the receptor—called PTP sigma—and studies in mice confirmed the connection.
“It’s hard to overcome CSPGs in the human body, but receptors may offer an easier target,” said Flanagan. “This discovery may lead to treatments that help repair spinal cord injury and may be beneficial to patients with brain injury and neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Lou Gehrig’s, multiple sclerosis and stroke.”
Students may contact John Flanagan at flanagan@hms.harvard.edu for more information.
Conflict Disclosure: The authors report no conflicts of interest.
Funding Sources: The National Institutes of Health; the authors are solely responsible for the content of this work.
