A lead on why lead hurts the brain.

Scores of studies have linked excessive lead exposure, especially during childhood, with mental retardation, growth defects, high blood pressure, and various other woes. As a result, the United States and many other countries have gone to great lengths to eliminate lead from gas, paints, window blinds, and many other products. At the same time, scientists have struggled to understand how this metal causes so many problems.

Christopher M.L. Bouton of the Johns Hopkins Medical Institutions in Baltimore and his colleagues may be on the verge of explaining, on a molecular level, how lead affects the brain. They report that the metal appears to bind to a cell-membrane molecule called synaptotagmin, which plays a key role in releasing chemical messages, or neurotransmitters, from nerve cells. Normally, calcium binds to synaptotagmin to control this secretion. "We think lead is binding to the same pockets where calcium ions usually sit," says Bouton.

Lead, however, doesn't trigger synaptotagmin to perform all the molecular actions that calcium prompts. The metal doesn't, for example, promote the binding of synaptotagmin to a protein called syntaxin, one of the steps that normally lead to a release of neurotransmitters. "It's an imperfect mimic," says Bouton. He and his coworkers believe that lead also targets calcium-binding pockets on other crucial proteins in nerve cells.