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Research Grants 2006

To view an abstract, select an author from the vertical list on the left.

2006 Grant - Kayed

Amyloids as Toxins: Probing Common Structural and Functional Properties

Rakez Kayed, Ph.D.
University of California
Irvine, California

2006 New Investigator Research Grant

The amyloid hypothesis of Alzheimer's disease suggests that abundance of a small protein called beta-amyloid is the initial step that starts the pathological process. Beta-amyloid molecules then assemble themselves to form larger structures, which culminate with amyloid plaques. Although these plaques are one of the hallmarks of the disease, recent evidence suggests that they are not, in fact, the most toxic form. That distinction falls upon the smaller oligomers, clusters of only a few beta-amyloid molecules.

These small beta-amyloid species are similar in shape to toxic proteins that are linked to other neurodegenerative diseases, such as Parkinson's disease. This has led to the hypothesis that a common generic structure may underlie different neurodegenerative pathologies.

Rakez Kayed, Ph.D. plans to test this hypothesis. He believes that the structure most likely responsible for toxicity is a protein oligomer that assumes a ring or donut shape. Such species might behave like similarly-shaped bacterial toxins that insinuate themselves into cell membranes where they act like pores, allowing leakage in and out of the cell.

To test this hypothesis, Kayed and colleagues have generated a unique kind of antibody. While antibodies normally recognize and bind to specific protein sequences, this antibody can bind to pore-like structures regardless of their protein sequence. This antibody not only reacts with pore-forming toxins but can also prevent their toxicity. Using the antibody to capture pore-like structures from autopsied brain tissue samples of people who had Alzheimer's disease, the researchers will investigate the formation and toxicity of the structures in neurons. Their findings could lead to new insights into the pathology of Alzheimer's disease and potential treatments.

Alzheimer's Association International Conference | July 16-20, 2017, London, England

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