Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 31 January 2020 / Approved: 3 February 2020 / Online: 3 February 2020 (05:45:33 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Int. J. Mol. Sci. 2020, 21, 1995
DOI: 10.3390/ijms21061995

Abstract

The amyloid fibril formation by $\alpha$-synuclein is a hallmark of various neurodegenerative disorders, most notably Parkinson's disease. Epigallocatechin gallate (EGCG) has been reported to be an efficient aggregation inhibitor of numerous proteins, among them $\alpha$-synuclein. Here we show that this applies only to a small region of relevant parameter space and that under some conditions, EGCG can 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 relevant changes in experimental conditions. Our results are important for the development of strategies to identify and characterise promising amyloid inhibitors.

Subject Areas

amyloid; α-synuclein; EGCG; inhibition

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