Researchers at the Fisher Center for Alzheimer's Disease Research laboratory today published "Gamma-secretase Activating Protein is a Therapeutic Target for Alzheimer's Disease" in Nature online. Drs. Gen He (lead author) and Paul Greengard have discovered a protein that stimulates the production of beta-amyloid, and therefore represents a major new advance in Alzheimer's disease research.
The protein, called gamma-secretase activating protein (gSAP), is expected to become a major target for anti-amyloid drugs that inhibit the brain's ability to produce toxic beta amyloid in Alzheimer's disease. Beta-amyloid is a substance found in the brain that becomes toxic in Alzheimer's disease and is responsible for most of the devastating symptoms of the disease. The researchers also discovered that gSAP is a target of the anti-cancer drug, Gleevec, which Fisher scientists previously showed could lower beta-amyloid levels in the brain. The new study showed that Gleevec lowers beta-amyloid production by binding to gSAP and preventing it from activating an enzyme called gamma-secretase, which is responsible for producing beta-amyloid. In addition, the researchers showed that the inhibition of gSAP is not toxic to nerve cells, unlike many other experimental beta-amyloid inhibitor drugs that produce severe toxic reactions. Hence, gSAP holds the promise of discovering highly specific anti-beta-amyloid drugs that will be safe to patients.
"Millions of people suffer from Alzheimer's disease, and treatment options are limited," says Dr. Paul Greengard, Nobel Laureate and Director of the Fisher Center for Alzheimer's Disease Research laboratory at The Rockefeller University. "Existing drugs may mask symptoms for a time but do nothing to stop the relentless downward progression of Alzheimer's. What is needed are safe and effective medications that will halt the cause of the underlying disease. It is our hope that this gamma-secretase activating protein will greatly add to the creation of safe and effective Alzheimer's treatments."
Kent Karosen, President of the Fisher Center for Alzheimer's Research Foundation says, "We are so proud of the scientists we support, and would like to specifically congratulate Drs. He and Greengard for discovering this important protein. Their latest research is a potential paradigm shift in how scientists and doctors around the world will attack Alzheimer's."
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