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2007 Grant - Bitan
Investigation of Beta-Amyloid Protein Oligomerization and Neurotoxicity
Gal Bitan, Ph.D.
University of California at Los Angeles
Los Angeles, California
2007 Investigator-Initiated Research Grant
Beta-amyloid is a protein fragment suspected of disrupting cell-to-cell communication and damaging cells in Alzheimer's disease. Beta-amyloid clumps together in stages, eventually forming amyloid plaques. Recent studies have shown, however, that a tiny cluster of a few beta-amyloid molecules, called an oligomer—a very early stage in this clumping process—may be the primary toxic element in Alzheimer's. However, little is known about how oligomers are formed and how they produce toxic effects on brain cells.
Gal Bitan, Ph.D., and colleagues have found that longer forms of beta-amyloid produce different aggregates than do shorter forms. This difference may account for the substantially higher toxicity of the longer forms. Moreover, evidence has shown that a distinct region of beta-amyloid may determine how the protein fragment produces toxic aggregates. Further research has indicated that another beta-amyloid region, which likely does not play a role in the formation of oligomers, does help determine the protein fragment's level of toxicity.
For this proposed study, Dr. Bitan's team will conduct detailed structural analyses of both of these beta-amyloid regions. They will then determine how structural modifications to the regions may affect (1) the toxicity of the beta-amyloid and (2) the aggregation of beta-amyloid. Results could lead to novel mechanism-based therapies for Alzheimer's disease.