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

Juan Miguel Lopez Del Amo; Uwe Fink; Muralidhar Dasari; Gerlinde Grelle; Erich E. Wanker; Jan Bieschke; Bernd Reif

doi:10.1016/j.jmb.2012.01.013

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

Juan Miguel Lopez Del Amo, Uwe Fink, Muralidhar Dasari, Gerlinde Grelle, Erich E. Wanker, Jan Bieschke, Bernd Reif

Associate Professorship of Solid-State NMR spectroscopy

Research output: Contribution to journal › Article › peer-review

150 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	517-524
Number of pages	8
Journal	Journal of Molecular Biology
Volume	421
Issue number	4-5
DOIs	https://doi.org/10.1016/j.jmb.2012.01.013
State	Published - 24 Aug 2012

Keywords

Alzheimer's disease
drug development
magic angle spinning (MAS) solid-state NMR spectroscopy
neurotoxicity
β-amyloid peptide

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10.1016/j.jmb.2012.01.013

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

abstract = "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.",

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author = "{Lopez Del Amo}, {Juan Miguel} and Uwe Fink and Muralidhar Dasari and Gerlinde Grelle and Wanker, {Erich E.} and Jan Bieschke and Bernd Reif",

note = "Funding Information: This research was supported by the Leibniz-Gemeinschaft and the Helmholtz-Gemeinschaft , the Deutsche Forschungsgemeinschaft , and the Bundesministerium f{\"u}r Bildung und Forschung (grants Bi1435 , Re1435 , SFB449 , SFB740 , and NGFN-Plus 01GS08132 ). We are grateful to the Center for Integrated Protein Science Munich for financial support. J.M.L.d.A. acknowledges a Deutsche Forschungsgemeinschaft postdoctoral stipend (Lo1546). ",

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AU - Wanker, Erich E.

AU - Bieschke, Jan

AU - Reif, Bernd

N1 - Funding Information: This research was supported by the Leibniz-Gemeinschaft and the Helmholtz-Gemeinschaft , the Deutsche Forschungsgemeinschaft , and the Bundesministerium für Bildung und Forschung (grants Bi1435 , Re1435 , SFB449 , SFB740 , and NGFN-Plus 01GS08132 ). We are grateful to the Center for Integrated Protein Science Munich for financial support. J.M.L.d.A. acknowledges a Deutsche Forschungsgemeinschaft postdoctoral stipend (Lo1546).

PY - 2012/8/24

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N2 - 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.

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

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