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Two cardiovascular proteins pose a double whammy in Alzheimer's
Date:12/21/2008

sect with a neuroscience group to study Alzheimer's disease," Miano said. "But there's a great deal of evidence to suggest that Alzheimer's disease is a problem having much to do with the vascular plumbing. And Rochester is the type of institution where partnerships like these are easy to strike up."

For 15 years Zlokovic's laboratory has focused on the molecular mechanisms regulating blood supply and the role of the blood-brain barrier in the development of Alzheimer's disease. It's not simply that reduced blood supply hurts brain cells by causing a shortage of oxygen and other nutrients. Rather, deterioration of blood flow seems to gum up the brain's ability to remove toxic amyloid beta.

Normally, amyloid is picked up efficiently by blood vessels that then whisk the toxic trash away. But in Alzheimer's disease, the system no longer is able to keep up with the body's production of the substance. The molecular trash accumulates, and Zlokovic and others believe the buildup kills brain cells.

The current work focuses on two proteins well known to cardiovascular researchers, SRF (serum response factor) and myocardin. The two work together within smooth muscle cells that line blood vessels to activate genes that are necessary for smooth muscle to function properly. SRF binds to certain snippets of DNA called CArG boxes and serves as an anchor, while myocardin piggybacks along and turns on the genes to which SRF sticks. Together they act as a master switch that determines whether smooth muscle cells contract one of many ways the body controls just how much blood is flowing in the body.

Two years ago, Zlokovic and Miano published a study showing that the two proteins are much more active in the blood vessels of brains of people with Alzheimer's disease than in people who do not have the disease. They showed that when they reduced the activity of the proteins, blood flow in the brain increased, and when the genes were more active, blood
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Contact: Tom Rickey
tom_rickey@urmc.rochester.edu
585-275-7954
University of Rochester Medical Center
Source:Eurekalert

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