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Open AccessArticle

The Aggregation Conditions Define Whether EGCG is an Inhibitor or Enhancer of α-Synuclein Amyloid Fibril Formation

1
Institute of Physical Biology, Heinrich-Heine-University, 40225 Düsseldorf, Germany
2
Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, 40225 Düsseldorf, Germany
3
Department of Biotechnology and Biomedicine, Technical University of Denmark, 2800 Lyngby, Denmark
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(6), 1995; https://doi.org/10.3390/ijms21061995
Received: 31 January 2020 / Revised: 3 March 2020 / Accepted: 11 March 2020 / Published: 14 March 2020
(This article belongs to the Special Issue Natural Inhibitors of Amyloid Aggregation)
The amyloid fibril formation by α -synuclein is a hallmark of various neurodegenerative disorders, most notably Parkinson’s disease. Epigallocatechin gallate (EGCG) has been reported to be an efficient inhibitor of amyloid formation by numerous proteins, among them α -synuclein. Here, we show that this applies only to a small region of the relevant parameter space, in particular to solution conditions where EGCG readily oxidizes, and we find that the oxidation product is a much more potent inhibitor compared to the unmodified EGCG. In addition to its inhibitory effects, EGCG and its oxidation products can under some conditions even accelerate α -synuclein amyloid fibril formation through facilitating its heterogeneous primary nucleation. Furthermore, we show through quantitative seeding experiments that, contrary to previous reports, EGCG is not able to re-model α -synuclein amyloid fibrils into seeding-incompetent structures. Taken together, our results paint a complex picture of EGCG as a compound that can under some conditions inhibit the amyloid fibril formation of α -synuclein, but the inhibitory action is not robust against various physiologically relevant changes in experimental conditions. Our results are important for the development of strategies to identify and characterize promising amyloid inhibitors. View Full-Text
Keywords: amyloid; EGCG; inhibition; kinetics; seeding; nucleation; Parkinson disease amyloid; EGCG; inhibition; kinetics; seeding; nucleation; Parkinson disease
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Sternke-Hoffmann, R.; Peduzzo, A.; Bolakhrif, N.; Haas, R.; Buell, A.K. The Aggregation Conditions Define Whether EGCG is an Inhibitor or Enhancer of α-Synuclein Amyloid Fibril Formation. Int. J. Mol. Sci. 2020, 21, 1995.

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