Research describes how nerve growth factor stimulates a sequence of proteins that promote nerve growth

Jul 1 2004

Scientists at the University of North Carolina at Chapel Hill have discovered key steps involved in regulating nerve growth and regeneration that may have implications for spinal cord research.

The new research, published in the June 24 issue of the journal Neuron, for the first time describes how nerve growth factor (NGF) stimulates a sequence of proteins – a molecular pathway – that promotes nerve growth.

"It is the first study to show the link between NGF and the building blocks that form the axon," said Dr. William Snider, professor of neurology and cell and molecular physiology at UNC’s School of Medicine and director of the UNC Neuroscience Center.

Axons are long tendrils, or processes, that extend from nerve cells to form connections with other nerve cells, muscles and the skin.

Injury to the peripheral nervous system – that portion of the nervous system outside the brain and spinal cord – typically results in spontaneous regeneration and repair. However, this is not the case with the spinal cord, where disruption of connections from injury leads to paralysis.

"The results of this study allow us to know more about how to promote axon growth and regeneration in the spinal cord," said Dr. Fengquan Zhou, a postdoctoral fellow of the Spinal Cord Research Foundation who works in Snider’s laboratory and is lead author of the study.

In addition, the findings may be important to understanding how the brain is wired, said Snider. "We think the findings may be relevant to axon growth in the brain."

In the study, Zhou took a novel approach to identifying missing links in the molecular pathway when he recognized that NGF stimulation occurred in the growth cone of the axon. This simplified a complex problem that had previously eluded others who did not focus on the growth cone.

Basically, in the pathway Zhou identified, NGF signals two proteins (PI3K and GSK-3beta and PI3K) that, in turn, regulate another protein, APC, to assemble the axon from its building blocks called microtubules.

"This work helps us understand how an axon is put together and gives us a new idea about how we might make it happen after a spinal cord injury."

The study was funded by a grant from the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health.

Co-authors with Zhou and Snider are Yaohong Wu, also of the UNC Neuroscience Center, and Dr. Shoukat Dedhar of the British Columbia Cancer Agency in Canada.

http://www.unc.edu/