2005 Grant - D'Adamio
Role of Membrane Proteins in APP Processing and Signaling
Luciano D'Adamio, M.D., Ph.D.
Albert Einstein College of Medicine
Bronx, New York
2005 Investigator-Initiated Research Grant
The beta-amyloid protein fragment, a key suspect in Alzheimer's disease processes, is released from the much larger amyloid precursor protein (APP). It is not yet clear why this occurs or what role the process might have in the normal and diseased brain. However, structural and behavioral similarities between APP and another well-studied protein called Notch, suggests that beta-amyloid might be released when APP binds to some specific protein partners called ligands.
Luciano D'Adamio, M.D., Ph.D., and colleagues recently identified a protein called CD74 as a potential ligand for APP. Both CD74 and APP are found bound to the membrane that surrounds cells, particularly neurons, and the researchers found that CD74 can interfere with the release of beta-amyloid.
To verify if CD74 is a true APP ligand, the researchers will study the interaction between the two proteins in depth. They will determine if CD74 is essential for beta-amyloid production by measuring the protein fragment's release from neurons that have had CD74 removed. They will also determine what parts of APP and CD74 are involved in their interaction. The information may be useful for the design of small molecules that could interfere with beta-amyloid production and serve as therapeutics for Alzheimer's disease.