Researchers Uncover Clues About Gateway To...( St. Louis March 30 1999 -- Scientis...),Health

St. Louis, March 30, 1999 -- Scientists have uncovered evidence about the workings of one of the gateways into the brain. Their findings suggest approaches to control the gateway with drugs, which could have implications for treating AIDS, depression, cancer and other diseases that affect the brain. Doctors have struggled to get many drugs across a main gateway to the brain known as the blood-brain barrier. But now, researchers have determined that a guardian protein called p-glycoprotein at this barrier collaborates with a similar protein to limit traffic through a second barrier to the brain. This structure, which lines cavities deep within the brain, is known as the choroid plexus.

"The choroid plexus may be a major surface of exchange for drugs traveling from the blood into the cerebrospinal fluid through this back-door barrier," says David Piwnica-Worms, M.D., Ph.D., professor of radiology and associate professor of molecular biology & pharmacology at Washington University School of Medicine in St. Louis. He is principal investigator of the study published in the March 30 issue of Proceedings of the National Academy of Sciences. Vallabhaneni V. Rao, Ph.D., a former instructor of radiology, was lead author of the study, which also involved collaborators at Yale University School of Medicine. Piwnica-Worms hopes to learn how to alter the properties of proteins that keep this back door shut. "It might be possible to enhance delivery of many drugs by blocking the transporter proteins at the choroid plexus in a selective and careful way," he says. These efforts might allow entry into the brain of the protease inhibitors that kill cells infected with HIV, for example. Some doctors think the brain serves as a safe haven for the virus, thwarting efforts to eradicate it.

The choroid plexus drew Piwnica-Worms' interest after images originally designed to highlight cancerous cells also revealed the tissue to be a potential location for the p-glycoprotein (Pg
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Contact: Barbra Rodriguez
rodrigub@medicine.wustl.edu
314-286-0122
Washington University School of Medicine
30-Mar-1999