Structural properties of EGCG-induced, nontoxic Alzheimer's disease Aβ oligomers.
The green tea compound epigallocatechin-3-gallate (EGCG) inhibits Alzheimer's disease β-amyloid peptide (Aβ) neurotoxicity. Solution-state NMR allows probing initial EGCG-Aβ interactions. We show that EGCG-induced Aβ 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 Aβ. The C-terminal part of the Aβ peptide (residues 22-39) adopts a β-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 Aβ aggregates as well. The structural analysis of small-molecule-induced amyloid aggregates will open new perspectives for Alzheimer's disease drug development.
Helmholtz-Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
Juan Miguel
JM
Lopez del Amo
Uwe
U
Fink
Muralidhar
M
Dasari
Gerlinde
G
Grelle
Erich E
EE
Wanker
Jan
J
Bieschke
Bernd
B
Reif
D000544:Alzheimer Disease / Q000139:chemically induced* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D002392:Catechin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018696:Neuroprotective Agents / Q000009:adverse effects* / Q000378:metabolism; D011487:Protein Conformation; D011489:Protein Denaturation; D055503:Protein Multimerization
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D002392:Catechin; C045651:epigallocatechin gallate