Structural characterization of the interaction between the Alzheimer's disease beta-amyloid peptide and the catechin EGCG

• Applicant: Professor Dr. Bernd Reif
• Subject Area: Structural Biology ; Biophysics
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 264855120

The green tea compound epigallocatechin-gallate (EGCG) inhibits Alzheimer's disease beta-amyloid peptide (A-beta) neurotoxicity. Upon titration of ECGG to A-beta, NMR chemical shift changes indicate an interaction between monomeric A-beta and EGCG. Oligomeric aggregates formed in presence of EGCG yield well defined MAS solid-state NMR spectra and show that these precipiates are accessible for a structural analysis. It is the aim of the proposal to characterize the interaction pathway from soluble complexes to the structure in the aggregated state. Oxidative conditions and effect of metals on the interaction will be tightly controlled. For that purpose, we employ a combination of solution-state and MAS solid-state NMR, as well as Dynamic Light Scattering (DLS), Small Angle X-Ray Scattering (SAXS), Electron Microscopy (EM) and Atomic Force Microscopy (AFM). Knowledge of the atomic structure of small molecule induced amyloid aggregates will aid to rationalize the structural basis of neurotoxicity, and at the same time open new perspectives for Alzheimer's disease drug development.

• DFG Programme: Research Grants