December 3, 2009
WATERTOWN, Mass.Combining two chemicals, one of which is the green tea component EGCG, can prevent and destroy a variety of protein structures known as amyloids that are primary culprits in fatal brain disorders such as Alzheimer's, Huntington's and Parkinson's diseases, according to researchers at the Boston Biomedical Research Institute (BBRI) and the University of Pennsylvania.
Amyloid plaques are tightly packed sheets of proteins that infiltrate the brain. The plaques, which are stable and seemingly impenetrable, fill nerve cells or wrap around brain tissues and eventually suffocate vital neurons or brain cells, causing loss of memory, language, motor function and eventually premature death.
Previous studies exposed amyloids in living yeast cells to EGCG. Researchers found that DAPH-12 also inhibits amyloid production in yeast. Researchers looked in more detail at the impact of these two chemicals on the production of different amyloids produced by the yeast amyloid protein known as PSI+. They chose this yeast amyloid protein because it has been studied extensively in the past, and because it produces varieties of amyloid structures that are prototypes of those found in the damaged human brain. Therefore, PSI+ amyloids are excellent experimental paradigms to study basic properties of all amyloid proteins.
The researchers first step was to expose two different amyloid structures produced by yeast to EGCG. They found that the EGCG effectively dissolved the amyloids in the weaker version. They also found that the stronger amyloids were not dissolved and that some transformed to even stronger versions after exposure to EGCG. They hen exposed the yeast amyloid structures to a combination of the EGCG and the DAPH-12 and found that all of the amyloid structures broke apart and dissolved.
The next steps for the research team will be to explore the mechanism and potency of such a combinatorial therapy for the treatment of diverse neurodegenerative diseases.
"Our findings are certainly preliminary and we need further work to fully comprehend the effects of EGCG in combination with other chemicals on amyloids. Yet, we see our study as a very exciting initial step toward combinatorial therapies for the treatment of amyloid-based diseases," the researchers wrote.
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