P&S Journal: Winter 1998, Vol.18, No.1
Estrogen and Alzheimer's
Increasingly, evidence shows that estrogen may help delay or prevent Alzheimer's disease. Unfortunately, estrogen is not without side effects: an increased risk of some cancers for women and feminizing effects for men. Now, new research by Dr. Dominique Toran-Allerand, professor of anatomy and cell biology in the centers for neurobiology and behavior and reproductive sciences, suggests the possibility of estrogen-like drugs that work to treat Alzheimer's disease without causing side effects.
Dr. Toran-Allerand is investigating exactly how estrogen sends signals in the brain. Current dogma suggests that estrogen acts by diffusing into cells and binding to receptors in the nucleus, which then go on to regulate various genes. But, says Dr. Toran-Allerand, estrogen also could share signaling pathways with neurotrophins, since their receptors exist in the same neurons. "Many genes that estrogen supposedly regulates don't have estrogen-responsive sequences in DNA," she says.So estrogen may use another way of getting a signal from the cell membrane to the nucleus.
In work presented at the 1996 and 1997 annual meetings of the Society for Neuroscience, Dr. Toran-Allerand and colleagues found that estrogen can quickly activate proteins that are part of the neurotrophin signaling pathway. Estrogen enters the cell and immediately activates certain cytoplasmic enzymes--extracellular-signal-regulated kinases or ERKs--that relay neurotrophin signals from the receptors at the cell surface to the nucleus.
Ideally, one could design a drug that would stimulate only the pathway specific to the brain, if there is one, but not pathways that lead to feminizing side effects, for instance. This would mean that men with Alzheimer's could be treated with the drug, she says.