New signaling pathway found, may be linked to movement disorders

St. Louis, July 11, 2002 Though previous evidence points to the contrary, scientists have discovered that the protein known as fibroblast growth factor 14 (FGF14) may not actually behave like a growth factor. The research suggests that FGF14 is instead involved in transmitting signals from one nerve cell to another and may help regulate walking and other movements. The protein could, therefore, be linked to movement disorders such as Parkinson's and Huntington's diseases.

"We believe we have found a new signaling pathway in the brain," says study leader David M. Ornitz, M.D., Ph.D., professor of molecular biology and pharmacology at Washington University School of Medicine in St. Louis. "Once we learn what FGF14 does at the molecular level, I believe we may uncover a new mechanism for regulating nerve cell function."

The work is published in the July 3 issue of the journal Neuron. It is the first study to examine the role of FGF14 in living animals and could provide new targets for testing future drugs designed to treat movement disorders and seizures, says Ornitz, who also leads the cancer and developmental biology program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

Ornitz and the team of investigators developed a strain of mice lacking the gene for FGF14. They expected these mice to have brain abnormalities and to perhaps die before birth. To their surprise, however, the mice seemed physically healthy and lived relatively normal lives, though most were about 15 percent under-weight after two weeks of age.

But the young mice did develop coordination problems and abnormal posture. Compared with normal mice, the genetically altered animals walked sluggishly and shuffled, and they had reduced muscle strength. They also were less sensitive to stimulants such as cocaine and amphetamines and were more prone to drug-induced seizures. The investigators also examined t

Contact: Darrell E. Ward
Washington University School of Medicine

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