Jun 12, 2002
NEW YORK (Reuters Health) - Scientists from the US and Germany have shown that the inhibitory effect of myelin-associated glycoprotein (MAG) on nerve regeneration is mediated by specific nerve cell surface gangliosides.
The discovery provides "new directions and tools" for studies of spinal cord injury and axon regeneration, they write in the June 11 issue of Proceedings of the National Academy of Sciences (PNAS).
"When damaged, nerve cells have the potential to reconnect, but regeneration is halted by inhibitory molecules released at the immediate site of the injury," lead researcher Dr. Ronald L. Schnaar, of The Johns Hopkins School of Medicine in Baltimore, told Reuters Health. MAG is one such inhibitory molecule.
In the PNAS paper, the researchers report that the neuronal gangliosides GD1a and GT1b are the natural ligands of MAG. Blocking ganglioside biosynthesis either pharmacologically or genetically attenuates MAG inhibition in cultured rat neurons and thereby improves nerve regeneration. Their experiments also suggest that ganglioside clustering is the first step in MAG-mediated neurite outgrowth inhibition.
"Since the structures of MAG and gangliosides are essentially the same between rats and humans, the knowledge gained is expected to apply equally to man," Dr. Schnaar said.
His group has begun studies in mice to determine if this approach can improve nerve regeneration after experimental injury. "There is long-term optimism in the field, but the barriers to nerve regeneration are many and profound," Dr. Schnaar said. "MAG is only one of at least three inhibitory molecules discovered at the site of nerve injury. Even if the inhibitory action of MAG is reversed, the other inhibitors may still limit nerve regeneration."
In a commentary, Dr. Lisa McKerracher of the Universit de Montr al, Qu bec, Canada, points out that the signal transduction pathway involving the activation of Rho, a small GTPase, "may be a convergent point for signaling by different inhibitory receptors." If so, then Rho signaling could "become an important therapeutic target to overcome growth inhibition in the CNS," she writes.
Proc Natl Acad Sci USA 2002;99:7811-7813,8412-8417.
© 2002 Reuters Ltd