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Needle-in-a-haystack search for new drugs for brain diseases

The scientific equivalent of searching for a needle in a haystack has paid off for researchers seeking leads for potential new medicines for Parkinson's Disease and other brain disorders.

Chronicled in a new episode in the American Chemical Society's award-winning "Global Challenges/Chemistry Solutions" podcast series, now online, it involved sifting through almost 390,000 chemical compounds. Finally, they located one that blocks formation of cholesterol in the brain.

Aleksey G. Kazantsev, Ph.D., and colleagues at MassGeneral Institute for Neurodegenerative Disease, previously discovered that blocking cholesterol formation in the brain could protect against some of the damage caused by chronic brain disorders like Parkinson's disease. Several other studies have suggested that too much cholesterol may kill brain cells in similar neurodegenerative diseases. So they launched a search for a so-called "small molecules" — substances ideal for developing into medicines — capable of blocking formation of cholesterol.

He reported the discovery of a small molecule that blocks the activity of a key protein involved in cholesterol production in the journal, ACS Chemical Biology. It successfully lowered cholesterol levels in isolated nerve cells and brain slices from mice. If the molecule proves to be a good target for developing new drugs, Kazabtse says, "it could have a broader application in other neurological conditions, such as Alzheimer's disease, for which modulation of cholesterol and other associated metabolic pathways might be of therapeutic benefit."

The new podcast is available without charge at iTunes and from ACS' website at

Global Challenges/Chemistry Solutions is a series of podcasts describing some of the 21st Century's most daunting problems, and how cutting-edge research in chemistry matters in the quest for solutions. Global Challenges is the centerpiece in an alliance on sustainability between ACS and the Royal Society of Chemistry. Global Challenges is a sweeping panorama of global challenges that includes dilemmas such as providing a hungry, thirsty world with ample supplies of safe food and clean water; developing alternatives to petroleum to fuel society; preserving the environment and assuring a sustainable future for our children; and improving human health. During the 2011 global celebration of the International Year of Chemistry (IYC), Global Challenges/Chemistry Solutions also is focusing on the main themes of IYC — health, environment, energy, and materials.

The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With more than 163,000 members, ACS is the world's largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

Michael Bernstein | EurekAlert!
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