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2010 Grants - Liebman
Yeast Cell-Based HTS Screen for Inhibitors of Abeta42 Oligomerization
Susan W. Liebman, Ph.D.
Board of Regents, NSHE, obo University of Nevada
2010 Investigator-Initiated Research Grant
Beta-amyloid (also known as Abeta) is a protein fragment that is toxic to nerve cells and which aggregates into amyloid plaque, one of the characteristic features of Alzheimer pathology. Recent research indicates that beta-amyloid is toxic only after it has formed small aggregates known as oligomers. Thus, the process of aggregate formation (oligomerization) is thought to be a key step in the disease process.
Susan W. Liebman, Ph.D., and colleagues have developed a sensitive biochemical test to detect when beta-amyloid molecules form oligomers. This test relies on the use of yeast cells and is capable of efficiently screening a large number of potential drugs for their ability to inhibit beta-amyloid oligomerization. The researchers have already screened more than 12,000 chemical compounds and they identified two that inhibit beta-amyloid oligomerization. They plan to continue screening in the hopes of identifying up to 10 potential drug candidates that can be further tested for their usability as drugs. The promising drug candidates will also be tested for their ability to inhibit beta-amyloid oligomerization in living cells, as well as in animal models of beta-amyloid toxicity. These studies represent an important step toward the identification of drugs that may slow or prevent the development of Alzheimer's disease in humans.