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UT Southwestern researchers create molecule that nudges nerve stem cells to mature
Date:6/15/2008

DALLAS June 15, 2008 Inspired by a chance discovery during another experiment, researchers at UT Southwestern Medical Center have created a small molecule that stimulates nerve stem cells to begin maturing into nerve cells in culture.

This finding might someday allow a person's own nerve stem cells to be grown outside the body, stimulated into maturity, and then re-implanted as working nerve cells to treat various diseases, the researchers said.

"This provides a critical starting point for neuro-regenerative medicine and brain cancer chemotherapy," said Dr. Jenny Hsieh, assistant professor of molecular biology and senior author of the paper, which appears online today and in the June 17 issue of Nature Chemical Biology.

The creation of the molecule allowed the researchers to uncover some of the biochemical steps that happen as nerve cells mature. It also showed that large-scale screening of compounds can provide starting points for developing drugs to treat disorders such as Huntington's disease, traumatic brain injury or cancer.

The scientists began this project as a result of a separate study in which they were screening 147,000 compounds to see which could stimulate stem cells cultivated from rodent embryos to become heart cells. Unexpectedly, five molecules stimulated the cells to transform into forms resembling nerve cells. The researchers then created a variation of these molecules, a new compound called Isx-9 (for isoxazole-9). Isx-9 was easier to use than its initially discovered relatives because it worked at a much lower concentration and also dissolved more easily in water.

"It was completely serendipitous that we uncovered this neurogenic [nerve-creating] small molecule," Dr. Hsieh said. "I think it's one of the most powerful neurogenic small molecules on the planet. In theory, this molecule could provoke full maturation, to the point that the new nerve cells could fire, generating the electric
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert

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Clone/PAD: ZMD.358. Immunogen: Synthetic peptide derived from the C-terminal region of human mouse and rat LRP5. Specificity: Reacts with human and mouse LRP5 proteins. Reactivity: Mouse Human (po
Replacement Parts for Electrophoresis Apparatus
Sprague-Dawley rats, 7-8 weeks old, mixed gender; tissue is collected fresh, frozen on dry ice within minutes of sacrifice and stored at -20C; individual tissue weight approx. 0.05 gram.
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