Paul Greengard, Ph.D., Vincent Astor Professor and head of the Laboratory of Molecular and Cellular Neuroscience at The Rockefeller University, has won the 2000 Nobel Prize in Physiology or Medicine for his discovery of how dopamine and a number of other transmitters in the brain exert their action in the nervous system. Last year's Nobel Prize in Medicine was awarded to Rockefeller University's Günter Blobel, M.D., Ph.D., John D. Rockefeller Jr. Professor and an investigator of the Howard Hughes Medical Institute.

Greengard shares the 2000 award with Arvid Carlsson, M.D., emeritus professor of pharmacology at the University of Göteborg in Sweden, and Eric Kandel, M.D., University Professor at Columbia University and senior investigator at the Howard Hughes Medical Institute.

Greengard, director of the Zachary and Elizabeth M. Fisher Center for Research on Alzheimer's Disease at Rockefeller, is a neuroscientist whose discoveries have provided a conceptual framework for understanding how the nervous system functions at the molecular level. He has also demonstrated that many effects — both therapeutic and toxic — of several classes of common antipsychotic, hallucinogenic and antidepressant drugs can be explained in terms of distinct neurochemical actions which affect the transmission of nerve signals in the brain.

Nerve cells, or neurons, in the brain communicate with one another by way of chemical substances called neurotransmitters. In one neuron, an electrical signal (a nerve impulse) causes the release of a neurotransmitter from its nerve terminal. A second neuron detects this neurotransmitter and responds by producing an electrical signal. This form of communication between two nerve cells is known as signal transduction.

Over the last 30 years, Greengard and his colleagues have developed a general model which provides a rational explanation, at the molecular and cellular levels, of the mechanism by which stimuli — both electrical and chemical — produce physiological responses in individual nerve

Paul Greengard and the members of the Laboratory of Molecular and Cellular Neuroscience.

cells. His research group and others have established that nerve cells respond to extracellular stimuli through an increase in the amount of a substance known as an intracellular ("second") messenger. Second messengers, in turn, produce many of their actions by regulating the activity of a family of enzymes called protein kinases. A protein kinase is an enzyme that attaches a phosphate molecule to a target protein. A phosphorylated protein, through one or more biochemical steps, produces the physiological response characteristic of the neurotransmitter.

Greengard and his group have found a large number of phosphorylated proteins that occur only in the brain. Of these, some are present in every nerve cell, and others in only one or a few cell types. These studies have demonstrated that various subclasses of neurons differ markedly from one to another in their chemical composition and suggest that it will be possible to develop highly specific therapeutic agents for the treatment of various neurological and psychiatric disorders.

Abnormalities in signaling by the neurotransmitter dopamine are associated with several neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, attention deficit hyperactivity disorder, and substance abuse. His lab has shown that a protein called DARPP-32 is a major player in the mechanisms by which dopamine produces its effects in the brain.

Greengard received a Ph.D. in biophysics from Johns Hopkins University in 1953. After postdoctoral studies in England at the University of London, Cambridge University, and the National Institute of Medical Research and at the National Institutes of Health, in Bethesda, Md., he became director of biochemical research at the Geigy Research Laboratories in 1959. In 1968, he was appointed professor of pharmacology at Yale University and was named Henry Bronson Professor in 1981. In 1983, he joined The Rockefeller University as a Vincent Astor Professor.

Greengard is an elected member of the U.S. National Academy of Sciences and its Institute of Medicine and of the American Academy of Arts and Sciences. He is also a foreign member of the Royal Swedish Academy of Sciences and a member of the Norwegian Academy of Science

Paul Greengard answers questions from reporters.

and Letters.

Among Greengard's many awards and honors are the 1999 Ellison Medical Foundation Senior Scholar Award, the 1998 Metropolitan Life Foundation Award for Medical Research and the 1997 Charles A. Dana Award for Pioneering Achievements in Health, which he shared with Kandel.

Support for Greengard's research over the years has come from many sources, including the National Institutes of Health, particularly the National Institute on Aging, the National Institute on Drug Abuse and the National Institute of Mental Health, and from the Zachary and Elizabeth M. Fisher Center for Alzheimer's Disease Research Foundation.

Greengard is married to the sculptor Ursula von Rydingsvard. They reside in New York City.

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