May 2, 2012 A highly toxic beta-amyloid a protein that exists in the brains of Alzheimer's disease victims has been found to greatly increase the toxicity of other more common and less toxic beta-amyloids, serving as a possible "trigger" for the advent and development of Alzheimer's, researchers at the University of Virginia and German biotech company Probiodrug have discovered.
The finding, reported in the May 2 online edition of the journal Nature, could lead to more effective treatments for Alzheimer's. Already, Probiodrug AG, based in Halle, Germany has completed phase 1 clinical trials in Europe with a small molecule that inhibits an enzyme, glutaminyl cyclase, that catalyzes the formation of this hypertoxic version of beta-amyloid.
"This form of beta-amyloid, called pyroglutamylated (or pyroglu) beta-amyloid, is a real bad guy in Alzheimer's disease," said principal investigator George Bloom, a U.Va. professor of biology and cell biology in the College of Arts & Sciences and School of Medicine, who is collaborating on the study with scientists at Probiodrug. "We've confirmed that it converts more abundant beta-amyloids into a form that is up to 100 times more toxic, making this a very dangerous killer of brain cells and an attractive target for drug therapy."
Bloom said the process is similar to various prion diseases, such as mad cow disease or chronic wasting disease, where a toxic protein can "infect" normal proteins that spread through the brain and ultimately destroy it.
In the case of Alzheimer's, severe dementia occurs over the course of years prior to death.
"You might think of this pyroglu beta-amyloid as a seed that can further contaminate something that's already bad into something much worse it's the trigger," Bloom said. Just as importantly, the hypertoxic mixtures that are seeded by pyroglu beta-amyloid exist as small aggregates, called oligomers, rather than as much larger fibers
|Contact: Fariss Samarrai|
University of Virginia