Small Molecule Triggers Nerve Cell Differentiation

A recent publication described the discovery of a small molecule that could stimulate cultures of stem cells to differentiate into nerve cells.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) had been screening a large number of compounds (more than 147,000) while searching for drugs that could stimulate stem cells to differentiate into cardiac tissue. Five of the compounds were found to be active, but in a different direction: they caused the stem cells to develop into nerve cells.

The investigators refined the structure of this group of molecules and created one, isoxazole-9 (Isx-9), that worked at a much lower concentration and dissolved more easily in water. They reported in the June 15, 2008, online edition of the journal Nature Chemical Biology that rodent nerve stem cells from the hippocampus cultured with Isx-9 clustered together and developed spiky appendages called neurites, which are typical of nerve cells growing in culture.

"It was completely serendipitous that we uncovered this neurogenic small molecule,” said senior author Dr. Jenny Hsieh, assistant professor of molecular biology the University of Texas Southwestern Medical Center. "I think it is 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 electrical signals needed for full functioning. This provides a critical starting point for neuro-regenerative medicine and brain cancer chemotherapy.”


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University of Texas Southwestern Medical Center