2005 New Investigator Research Grant

Phytoestrogens are naturally occurring plant chemicals which can mimic some of the actions of the hormone estrogen. Because there are indications that estrogen can protect nerve cells, there is considerable interest in phytoestro-gens as potential drugs for treating Alzheimer’s and other neurodegenerative diseases.

Liqin Zhao, Ph.D., and colleagues plan to investigate which phytoestrogens, or combination of phytoestrogens, may provide the best therapeutic benefit. One factor that needs to be considered is the affinity of the phytoestrogens towards receptors, or “docking sites” on the surface of cells. There are two estrogen receptors, alpha and beta, in the human brain. Evidence suggests
that estrogen can only have a neuroprotective effect when it binds to alpha receptors.

Zhao and colleagues hypothesize that phytoestrogens that selectively bind to alpha receptors might be a better drug than one that binds equally well to both alpha and beta receptors. The also posit that a combination of phytoestrogens might prove more effective than a single molecule.

To test these theories, the scientists plan to search for phytoestrogens from a pool of natural molecules and test their ability to protect neurons. In studies with animals, they will also determine whether these molecules will be able to penetrate the brain’s defenses and how they might affect the uterus and breast, organs that are extremely sensitive to the action of estrogens. Outcomes of this work may demonstrate the utility of developing estrogen-like therapies for Alzheimer’s disease.