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2006 Grant - Hall
A Proposed Mechanism for Amyloid Toxicity
James E. Hall, Ph.D.
University of California
2006 Investigator-Initiated Research Grant
Beta-amyloid is a small protein fragment that is suspected of being toxic to neurons in Alzheimer's disease. But exactly how that toxicity manifests itself is poorly understood. Beta-amyloid fragments assemble themselves into distinct structures, ultimately forming the plaques that are a hallmark of Alzheimer's. But which of these different species are toxic and in what way? Researchers have been desperately trying to answer these questions.
James Hall, Ph.D., plans to investigate one particular form of toxicity that has been attributed to beta-amyloid-the disruption of the cell membrane. While the integrity of the cell membrane is crucial for cell survival, there are indications that some forms of beta-amyloid polymers insinuate themselves into cell membranes, causing them to leak.
One theory suggests that these membrane-disruptive species of beta-amyloid change the conductance across the membrane so that the balance of electrically charged ions and other small molecules in the cell is altered. Hall and colleagues plan to test this hypothesis by first examining the effect of these beta-amyloid species on synthetic membranes, then determining how they affect conductance across intact cell membranes. The findings could lead to a new understanding of beta-amyloid toxicity and suggest new directions for future drug development.