University of California, Los Angeles (UCLA)

Solid-supported EPR: A Novel Approach to Study Beta-Amyloid Structures

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Alzheimer’s disease, a fatal neurodegenerative disease, is the most common form of dementia, afflicting more than five million Americans. Most of the patients are over age 65. Increasing age is the greatest known risk factor. Currently there is no cure for Alzheimer’s disease. Amyloid β protein is a small protein fragment that plays a central role in the development of Alzheimer’s disease. Self-association of β-amyloid to form larger assemblies is believed to trigger Alzheimer’s disease. Therefore, understanding the process of β-amyloid self-association and characterizing various β-amyloid assemblies are essential for elucidating the mechanism of Alzheimer’s disease and developing effective therapeutics. Because different β-amyloid assemblies co-exist, it is challenging to study individual species of β-amyloid assemblies with conventional techniques. New approaches addressing this challenge are still lacking.

In this project, we will develop a novel approach called solid-supported EPR to study β-amyloid structures. In the solid-supported approach, β-amyloid proteins are attached to a solid support, thus preventing β-amyloid self-association. As a result, β-amyloid can exist in a uniform state, making it unambiguous to interpret the experimental results. EPR stands for electron paramagnetic resonance, a technique for studying unpaired electrons. EPR is a powerful technique for studying protein structure, folding, and protein-protein interactions, with some unique advantages over other techniques. The combination of solid support and EPR will create a new powerful research tool to investigate β-amyloid proteins. Success in this project will contribute new insights into the mechanism of Alzheimer’s disease. The solid-supported EPR approach can also be used to study other neurodegenerative diseases.