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Structural properties of EGCG-induced, nontoxic Alzheimer's disease Aβ oligomers

Item Type:Article
Title:Structural properties of EGCG-induced, nontoxic Alzheimer's disease Aβ oligomers
Creators Name:Lopez Del Amo, J.M. and Fink, U. and Dasari, M. and Grelle, G. and Wanker, E.E. and Bieschke, J. and Reif, B.
Abstract:The green tea compound epigallocatechin-3-gallate (EGCG) inhibits Alzheimer's disease {beta}-amyloid peptide (A{beta}) neurotoxicity. Solution-state NMR allows probing initial EGCG-A{beta} interactions. We show that EGCG-induced A{beta} oligomers adopt a well-defined structure and are amenable for magic angle spinning solid-state NMR investigations. We find that EGCG interferes with the aromatic hydrophobic core of A{beta}. The C-terminal part of the A{beta} peptide (residues 22-39) adopts a {beta}-sheet conformation, whereas the N-terminus (residues 1-20) is unstructured. The characteristic salt bridge involving residues D23 and K28 is present in the structure of these oligomeric A{beta} aggregates as well. The structural analysis of small-molecule-induced amyloid aggregates will open new perspectives for Alzheimer's disease drug development.
Keywords:Alzheimer's Disease, {beta}-Amyloid Peptide, Magic Angle Spinning (MAS) Solid-State NMR Spectroscopy, Drug Development, Neurotoxicity
Source:Journal of Molecular Biology
Page Range:517-524
Date:24 August 2012
Official Publication:https://doi.org/10.1016/j.jmb.2012.01.013
PubMed:View item in PubMed

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