The anti-cancer drug Gleevec has been shown to disable a newly discovered key protein linked to the development of Alzheimer’s. The protein, gSAP, stimulates production of toxic beta-amyloid which is linked to the development of plaques in the brain typically associated with Alzheimer’s disease.
Dr. Gen He and Dr. Paul Greengard, both of the Fisher Center for Alzheimer’s Disease Research, have identified gamma secretase activating protein (gSAP). They’ve found that gSAP stimulates an enzyme called gamma secretase that is responsible for producing beta-amyloid. The researchers also discovered that the anti-cancer drug Gleevec binds to gSAP, preventing it from activating gamma secretase.
He and Greengard had previously found that Gleevec lowers levels of beta-amyloid in the brain by blocking the activity of gamma secretase. What they hadn’t previously understood was how Gleevec worked. Was Gleevec affecting gamma secretase directly or was it affecting gamma secretase indirectly through another protein?
“I was researching the mechanism of Gleevec’s effect of lowering amyloid,” Dr. He said in an interview for an article on Alzinfo.org. “My preliminary results indicated that Gleevec works by indirectly inhibiting gamma secretase. Therefore, I started to search for a specific protein that is targeted by Gleevec and regulates gamma secretase activity. This is how gSAP was found.”
The process of inhibiting gSAP is not toxic to nerve cells or other body cells, an important difference as other experimental treatments that inhibit beta-amyloid have proven to be toxic. Dr. He says, “We are working on selecting more potent drug-like compounds that selectively target gSAP and reduce plaques in experimental animal models; hopefully this will provide new treatments for Alzheimer’s.”
The work of these scientists now offers the potential to guide the development of effective and safe drugs that could treat the underlying cause of Alzheimer’s disease. This fresh knowledge seems to offer a step forward in finding a method to stop or slow the progression of the disease.
Greengard and He’s findings were published in the September 2, 2010 edition of the journal Nature.
Alzinfo.org. gSAP: A Key Protein in Plaque Formation Retrieved from http://www.alzinfo.org/07/alz-guide/gsap-key-protein
(September 2, 2010) Nature. Retrieved from http://www.nature.com/nature/outlook/alzheimers/index.html