2002-06-11 13:01:00 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Scientists have identified a pair of molecules that seem to play a role in keeping nerves from regenerating after being damaged. The signals that keep nerves from repairing themselves are complex and these two molecules, known as gangliosides, are not the only ones involved, but the discovery "provides new directions and tools" for unraveling the process, according to the study's authors.
In adult mammals, damaged nerves in the brain and spinal cord rarely regenerate, in part because of inhibitors on the surface of myelin, the thin, protective coating that insulates nerve fibers in the brain and spine. Once these inhibitors bind with receptors on the surface of nerve cells, signals that keep nerves from regenerating are released. Blocking this signaling pathway would represent a new approach for repairing nerves after an injury, but only some of the receptors that the inhibitors attach to have been discovered.
Now, a team led by Dr. Ronald L. Schnaar at the Johns Hopkins School of Medicine in Baltimore, Maryland, has identified two molecules called gangliosides that act as receptors for an inhibitor called MAG. Once MAG attaches to its receptors, the gangliosides may activate a signaling pathway called Rho, which blocks the growth of nerve-cell connections called axons.
In experiments with cultured rat brain cells, Schnaar's team found that altering the genes of gangliosides kept MAG from blocking nerve regeneration. Interfering with the accumulation of the receptors also kept MAG from doing its job. And the researchers confirmed that a flu drug called neuraminidase interfered with this process as well.
Schnaar and colleagues report their findings in the June 11th issue of the Proceedings of the National Academy of Sciences.
Despite the encouraging results in the lab, Schnaar told Reuters Health, "Our work is basic science and does not have any immediate impact on medicine." He and his colleagues have begun studies to see whether they can improve nerve regeneration in mice.
But Schnaar cautioned, "MAG is only one of at least three inhibitory molecules discovered at the site of nerve injury." Even if MAG can be blocked, the other inhibitors may prevent nerves from regenerating, he said.
Schnaar said he is optimistic that new therapies for repairing nerves will eventually develop, but he added, "The barriers to nerve regeneration are many and profound."
The identification of receptors for MAG is "another step forward" in the study of spinal cord injury and regeneration in the nervous system, according to Dr. Lisa McKerracher at the University of Montreal in Canada. The discovery of these receptors may identify a target for therapies that encourage repair in the central nervous system, she notes in a related editorial.
SOURCE: Proceedings of the National Academy of Sciences 2002;99:7811-7813,
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