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Paul Greengard in 1987.
Neurobiologist Paul Greengard, a Nobel laureate who has been diagnosed with neuronal and psychiatric diseases, died Wednesday, April 13, at the age of 93. Greengard joined The Rockefeller University Faculty in 1983, and was Vincent Astor Professor and Director of the Fisher Center for Alzheimer's Disease Research.
When Greengard began his career in the 1950s, he believed that nerve transmission was purely electrical, with nerve cells communicating exclusively through neurotransmitters that triggered electrical impulses in their neighbors. Biologists who studied the brain are of particular interest in the electrical properties of its specialized nerve cells, or neurons.
Bucking convention, Greengard, et al. Over the course of 15 years, Greengard demonstrated that this alternate signaling method, as it is known to slow synaptic transmission, is in fact the predominant means by which neurons communicate with one another-an accomplishment that led to its sharing the Nobel Prize in Physiology or Medicine. in 2000.
"Paul was an iconic scientist whose extraordinary seven-decade career was transformed into the understanding of neuroscience," says Richard P. Lifton, Rockefeller's president. "His discoveries laid out a new paradigm requiring the understanding of the biochemistry of nerve cells rather than simply their electrical activities. This work has had great impact. Psychiatric disorders, Parkinson 's disease, schizophrenia, depression, attention deficit hyperactivity disorder, and substance abuse.
Beginning in the Late 1960s, Greengard demonstrated that the neurotransmitter dopamine acts by inducing the formation of cyclic AMP in the post-synaptic neuron, which stimulates downstream enzymes known as protein kinases, resulting in chemical modification of specific protein substrates and thereby modifying their functions. This signaling process is similar to the mechanism used in the endocrine system to regulate various aspects of metabolism such as storage of glucose by the liver. In particular, this signaling modulates various aspects of neuronal function including receptor and neurotransmitter release.
Other neurotransmitters have been found to activate similar types of biochemical pathways. And because each neuron receives neurotransmitters from many different nerve cells, the form of biochemical communication has increased.
Having established by the early 1980s how to be more neuronal communication actually occurs, Greengard set about exploring how to aberrate in specific pathways might lead to various brain disorders. At the same time, he began investigating the molecular basis by which the drugs used to treat their conditions. His work greatly improves our understanding of neurological and psychiatric disorders, and points out the way towards new types of drugs to treat them.
Later in his career, Greengard elucidated the pathways responsible for producing the characteristic plaques that form in the brains of people with Alzheimer's. Alzheimer's and Parkinson's diseases are also vulnerable to these devastating neurodegenerative diseases.
Paul Greengard was born in New York City on December 11, 1925. A gift for maths and physics surfaced early, and upon enlisting in the Navy in 1943, Greengard was sent to MIT at the age of 17 to help develop a radar-based early Japanese kamikaze airplanes from destroying American ships in the Pacific.
After earning a B.S. in Physics at Hamilton College on the G.I. Bill, Greengarde But the only graduate fellowships in the field came from the Atomic Energy Commission, and Greengard did not wish to work on nuclear weapons. "I thought there were better ways of spending my life than trying to destroy mankind," he told an interviewer. The parents of his college suggested the emerging field of medical physics instead, and his race was set.
An invitation from the pioneering biophysicist Detlev Bronk, who would go to be president of Rockefeller, led Greengard to Johns Hopkins University, where he completed his Ph.D. in biophysics in 1953. Greengard then spent five years in England doing postdoctoral work at the University of London, Cambridge University, and the National Institute for Medical Research.
Upon returning to the United States, Greengard conducted research at the NIH; directed the department of biochemistry in the research laboratory of the giant Geigy (now Novartis); and taught at Vanderbilt University School of Medicine, the Albert Einstein College of Medicine, and the Yale University School of Medicine. In 1983 he came to Rockefeller, where he established the Laboratory of Molecular and Cellular Neuroscience and served as the founding director of the Fisher Center for Research on Alzheimer's Disease.
With his wife, the renowned sculptor Ursula von Rydingsvard, Greengard used the full sum of his Nobel Prize money to create an award for outstanding women in biomedical research. Greengard named after his mother, Pearl Meister Greengard, who died giving birth to him; and he hoped it would increase the likelihood that women would receive their fair share of the highest honors in science.
Greengard is survived by his wife Ursula von Rydingsvard; sister Linda Greengard; Claude and Leslie Greengard and daughter Ursula von Rydingsvard; and six grandchildren: Daniel, Philip, and Annie Greengard and Natasha Delfine and Emerson Greeve.
For more on Greengard's life and research, see this video, part of the Rockefeller oral history project.
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