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SFVAMC/UCSF researchers develop lead for a new Alzheimer's disease drug - a fragment of a brain growth protein

In findings that could lead to a new Alzheimer's disease drug, researchers at San Francisco Veterans Affairs Medical Center (SFVAMC) and University of California, San Francisco have isolated a protein fragment that nurtures brain cells, an effect that could prevent loss of brain function caused by the disease.

The fragment acts through the same mechanisms as its larger parent protein. However, a drug based on the fragment would be small enough to pass from the bloodstream into the brain, the researchers said.

These findings were presented today (November 8) in New Orleans at the 30th Annual meeting of the Society for Neuroscience, the world's largest neuroscience meeting.

The fragment is derived from a protein called Nerve Growth Factor (NGF), which maintains the health of many types of brain cells, including those damaged by Alzheimer's disease; it also helps strengthen the connections between cells.

But NGF can't be used as a treatment because the molecule is too large to get past the filtering mechanisms that protect the brain from bacteria and other agents in the blood that might damage it, said Frank Longo, MD, PhD, a UCSF professor and vice chair of neurology and SFVAMC chief of research.

Longo and his colleagues now have found that a much smaller portion of NGF may carry NGF's most useful functions.

"These studies offer the first demonstration that a small molecule mimicking a specific part of the NGF protein can activate the same key mechanisms in neurons that are activated by NGF, and in doing so prevent death of these neurons. Prior to this work, it was widely believed that the entire NGF protein was required to achieve its death-preventing activity," Longo said.

Other researchers had determined which sections of the NGF molecule dock to NGF receptors. Longo and his colleagues were hopeful that if they isolated these receptor-binding pieces, one of them might nurture nerve cells in the same way as the wh
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Contact: Kevin Boyd
kboyd@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
7-Nov-2000


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