Beating the brain's bouncer

Three research teams have developed new insights into the structure and function of the chief gatekeeper at the blood brain barrier-a multipurpose small molecule transporter called P-glycoprotein. The transporter has long been a bugbear to CNS drug makers, expelling otherwise potent compounds before they reach their targets. The findings provide a roadmap for the rational design and screening of small molecules that could hop the barrier.

P-glycoprotein (ABCB1; MDR; P-gp) is a transmembrane protein found in the endothelial cells of the brain's vasculature, where it pumps out a range of foreign compounds that seep in from the blood (see "Breaking through the blood brain barrier"). "The P-glycoproteinis the biggest culprit in pumping drugs out of the brain and has been the target for drug development for decades," said Ryan Watts, head of neurodegeneration research at the Genentech Inc. subsidiary of Roche...