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2008 Grants - Tessier
Molecular Mechanisms of Abeta Aggregation Inhibitors
Peter M. Tessier, Ph.D.
Rensselaer Polytechnic Institute
Troy, New York
2008 New Investigator Research Grant
Beta-amyloid (also known as Abeta) is a protein fragment that aggregates into structures that may be the key toxic factors in Alzheimer's disease. One approach being studied for treatment of Alzheimer's disease is the use of drugs that prevent beta-amyloid from aggregating. Chemicals known as polyphenols have shown promise as inhibitors of beta-amyloid aggregation. However, the molecular mechanisms of their actions are not well understood. Thus, it may take many years of trial-and-error testing before an ideal drug can be developed.
Peter M. Tessier, Ph.D., and colleagues are studying how polyphenols and related chemicals bind to beta-amyloid and prevent its aggregation. The goal of their study is to understand the precise molecular mechanisms of aggregation. Such knowledge would permit the rational design of optimal drugs to prevent aggregation, thereby avoiding the time-consuming trial-and-error process.
Dr. Tessier and colleagues will use a technique they have developed called peptide microarrays. Peptides are short sequences of protein-like molecules. The researchers will create large arrays of peptides related to segments of beta-amyloid and then use these arrays to study how beta-amyloid fragments bind together. They will then study how polyphenols disrupt such binding.
These studies may provide fundamental information about the chemical structures that mediate aggregation of beta-amyloid and the chemical structures of polyphenols that disrupt aggregation. Such information would be invaluable for the design of drugs that block or reverse beta-amyloid aggregation, potentially leading to new drugs to slow or halt the progression of Alzheimer's disease.