B-Amyloid Peptide/a2 Macroglobulin Interactions

Steven Gonias, MD, PhD University of Virginia

Project Details

Recent studies suggest that if the clearance of amyloid beta from the extracellular spaces of the brain is enhanced (through a vaccine), the progression of Alzheimer's disease (AD) may be stopped or reversed. A protein called a2-Macroglobulin (a2M) is a naturally occurring protein present in human blood and in the spaces between cells. This large protein contains a number of distinct binding sites for other, smaller proteins, including a binding site for growth factors near the center of the a2M structure. By binding growth factors, a2M may harm cells and increase cell death when excessive amyloid beta is present. Dr. Gonias has evidence suggesting that there is a distinct region in the structure of a2M that binds Alpha-beta. His goal is to further define the Alpha-beta binding site in a2M, with the long-range goal of identifying a2M miniproteins to mediate Alpha-beta catabolism and counteract the toxic activity of Alpha-beta. This study is a continuation of a project launched in 1999.