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.