Researchers have taken a giant step forward in learning hownerve growth factor (NGF) promotes nerve cell survival andtriggers cells to differentiate into neurons.
Three papers in today's Science and one in Thursday's Natureshed light on the way NGF activates cells.
The results are important to companies, such as Genentech Inc.and Synergen Inc., that are developing NGF as a therapeuticagent to treat nervous disorders.
Several years ago, scientists identified a 75-kilodalton (kd)molecular weight receptor that bound weakly to NGF. Sinceresearchers believed that NGF worked by binding tightly to areceptor, they have searched either for a second receptor or fora component that worked with 75kd to bind NGF tightly.
Now, researchers from the National Cancer Institute-FrederickCancer Research and Development Center in Frederick, Md., andCornell University in New York have shown that NGF binds toand activates a protein called Trk, which occurs on the surfaceof nerve cells.
The NCI-Cornell group showed that Trk and NGF bound weakly,but that cells containing both the Trk and 75kd receptorsbound to NGF with high affinity, suggesting that the tworeceptors work together to mediate NGF's actions.
The scientists speculate that other Trk-like receptors will befound that bind to the NGF-related peptides, brain-derivedneurotrophic factor (BDNF) and neurotrophic factor 3 (NT-3).Amgen Inc. and Regeneron Pharmaceuticals Inc. have formed apartnership to develop BDNF- and NT-3-based therapies.
Researchers from the National Institute of Allergy andInfectious Diseases and NCI expressed Trk on the surface offrog eggs. They showed that NGF stimulated Trk-containingeggs to mature. While this does not prove that NGF's binding toTrk is sufficient to promote neuron differentiation, it does showthat Trk alone can mediate some of NGF's actions.
-- Carol Talkington Verser, Ph.D. Special to BioWorld
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