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New clue to nerve growth may help regeneration efforts

Johns Hopkins scientists have discovered how one family of proteins repels growing nerves and keeps them properly on track during development. The finding, described in the Dec. 16 issue of Neuron, might provide a chance to overcome the proteins' later role in preventing regrowth of injured nerves, the researchers say.

The proteins, known as chondroitin sulfate proteoglycans (CSPGs), have long been known to prevent nerve regeneration after injury by recruiting a stew of other proteins and agents, but exactly what part of the mix keeps nerves from regrowing is unknown.

In studies of nerve growth in developing rats, the Hopkins scientists have linked CSPGs' no-growth effects to a protein called semaphorin 5A. The scientists, including David Kantor, an M.D./Ph.D. candidate, found that when CSPGs bind to semaphorin 5A, growing nerves are stopped in their tracks. Blocking this particular interaction freed the nerves to continue growing.

"CSPGs are a critical obstacle to nerve regeneration after injury, and without details about what's really happening, it's impossible to rationally intervene," says study leader Alex Kolodkin, Ph.D., professor of neuroscience in Johns Hopkins' Institute for Basic Biomedical Sciences. "We studied nerve growth, rather than re-growth, but our work provides a starting point for identifying more partners of CSPGs and for finding targets to try to counter these proteins' effects in nerve regeneration."

Semaphorins, including 5A, are a family of proteins that help direct growing nerves as they extend toward their eventual targets, largely by keeping nerves out of places they shouldn't be.

"These proteins are classic 'guidance cues' for nerves. There's nothing particularly fancy about what they do -- they bind to spots on the tip of the growing nerve, and the nerve doesn't continue going in that direction," says Kolodkin, whose lab studies semaphorins. "Scientists studying CSPGs' effects haven't rea
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
15-Dec-2004


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