The new findings, reported in the April 5 issue of The Journal of Biological Chemistry, provide the first step-by-step explanation of how estrogen prevents senile plaque build-up. Several groups, including Greengard’s, then showed that estrogen administration resulted in similar reductions in this protein in animal models of Alzheimer’s disease. In the late 1990s, Greengard’s laboratory was the first to demonstrate that estrogen reduces the production of the protein which accumulates to form these plaques using mouse, rat and human neurons. Most researchers believe these plaques are the cause of the disease. “These results suggest a new approach in the development of therapeutic agents for the treatment of Alzheimer’s disease,” says Greengard, Vincent Astor Professor and director of Rockefeller University’s Fisher Center for Alzheimer Research.Īlzheimer’s – whose devastating effects include memory loss, dementia and ultimately death – is characterized by these so-called senile plaques that build up in the brain. The results, derived from mouse cell lines and primary cultures from rat and human neurons, may have clinical applications for Alzheimer’s prevention in women.
This finding, by scientists in the laboratory of Rockefeller University Nobel laureate Paul Greengard, Ph.D., along with colleagues at Weill Medical College of Cornell University, provides evidence that the speed of a pathway can change the metabolic fate of a protein. Above, a neuron from the cortical region of a rat brain shows APP predominantly localized in the Golgi compartment (bright area).Įstrogen prevents the build-up of Alzheimer’s disease’s “senile plaques” in the brain by scooting key proteins through their normal pathways before they can form the debilitating plaques.
Researchers in Paul Greengard's laboratory have shown that the hormone estrogen stimulates the passage of amyloid precursor proteins (APP)-which contribute to the formation of senile plaques found in Alzheimer's disease-through a part of the cell known as the trans-Golgi network, thus reducing beta-amyloid formation in that compartment.