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2006 Grant - DeLisa
Natural Product-Like Compounds That Inhibit Intracellular Abeta Aggregation
Matthew P. DeLisa, Ph.D.
Ithaca, New York
2006 New Investigator Research Grant
Beta-amyloid protein fragments, key suspects in Alzheimer pathology, have a propensity to stick to each other. Small clusters of beta-amyloid inside neurons may exert the toxic effect that sets in motion Alzheimer's disease processes. A possible therapeutic approach would be to create a compound that either stabilizes beta-amyloid molecules so that they do not stick to each other or destabilize the small clusters so that they come "unglued."
Challenges that have been encountered in this include the structural properties of beta-amyloid that result in remarkably strong sticking power and the likelihood of synthetic compounds to react with cellular components that should be left alone.
One possible solution is the use of small molecules found in nature, often called "natural products," which have typically spent time inside of a cell during the course of evolution and are less likely to interact in a manner that damages cellular components such as membranes or DNA. In addition, recent studies have shown that many natural products are quite effective at inhibiting a diverse array of protein-protein assemblies.
Matthew P. DeLisa, B.S., and colleagues are exploring whether they can isolate natural products or natural product-like compounds with therapeutic potential. The investigators will use a cell-based experimental model to screen natural product-like compounds for their ability to disrupt beta-amyloid assembly. Their findings may lay the groundwork for future tests of promising candidate compounds in animal studies.