The Utility of NMR in the Design of B-Amyloid Inhibitors
Principal Investigator
Project Summary
The production of amyloid plaque from single molecules of Ab42 appears to go through predictable steps, beginning with the accumulation of larger, soluble Ab complexes that undergo changes that result in the formation of insoluble plaques. These steps are accompanied by structural changes in the individual Ab42 molecules into a form called a beta-sheet. Dr. Zagorski is applying Nuclear Magnetic Resonance imaging to study structural changes in Ab42 as well as other molecules known to inhibit amyloidosis. This information will then be used to construct three-dimensional models of Ab42 and inhibitors. These models should in turn allow for the design of better inhibitors of Ab accumulation that could help develop better treatments or even a prevention of AD.
Publications
Hou, L., Shao, H., Zhang, Y., Li, H., Menon, N.K., Neuhaus, E.B., Brewer, J.M., Vitek, M.P., Makula, R.A., Przybyla, A.B., and Zagorski, M.G. (2004) Solution NMR studies of the A beta(1-40) and A beta(1-42) peptides establish that the Met35 oxidation state affects the mechanism of amyloid formation. J. Am Chem Soc. 126(7):1992-2005 
Poeggeler, B., Miravalle, L., Zagorski, M.G., Wisniewski, T., Chyan, Y.J., Zhang, Y., Shao, H., Bryant-Thomas, T., Frangione, B., Ghiso, J., and Pappolla, M. (2001) Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Abeta peptide. Biochemistry. 40(49):14995-5001. [Alzforum Recommended Paper]
First published on: June 11, 2008
Last modified on: November 24, 2024