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Open AccessArticle

The Environment Is a Key Factor in Determining the Anti-Amyloid Efficacy of EGCG

1
Institute of Biothechnology, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania
2
Institute of Physical Biology, Heinrich-Heine-University, 40225 Düsseldorf, Germany
3
Department of Biotechnology and Biomedicine, Technical University of Denmark, DK-2800 Kgs Lyngby, Denmark
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2019, 9(12), 855; https://doi.org/10.3390/biom9120855
Received: 16 October 2019 / Revised: 6 November 2019 / Accepted: 6 December 2019 / Published: 11 December 2019
Millions of people around the world suffer from amyloid-related disorders, including Alzheimer’s and Parkinson’s diseases. Despite significant and sustained efforts, there are still no disease-modifying drugs available for the majority of amyloid-related disorders, and the overall failure rate in clinical trials is very high, even for compounds that show promising anti-amyloid activity in vitro. In this study, we demonstrate that even small changes in the chemical environment can strongly modulate the inhibitory effects of anti-amyloid compounds. Using one of the best-established amyloid inhibitory compounds, epigallocatechin-3-gallate (EGCG), as an example, and two amyloid-forming proteins, insulin and Parkinson’s disease-related α -synuclein, we shed light on the previously unexplored sensitivity to solution conditions of the action of this compound on amyloid fibril formation. In the case of insulin, we show that the classification of EGCG as an amyloid inhibitor depends on the experimental conditions select, on the method used for the evaluation of the efficacy, and on whether or not EGCG is allowed to oxidise before the experiment. For α -synuclein, we show that a small change in pH value, from 7 to 6, transforms EGCG from an efficient inhibitor to completely ineffective, and we were able to explain this behaviour by the increased stability of EGCG against oxidation at pH 6. View Full-Text
Keywords: insulin; α-synuclein; inhibition; EGCG; amyloid aggregation insulin; α-synuclein; inhibition; EGCG; amyloid aggregation
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MDPI and ACS Style

Sneideris, T.; Sakalauskas, A.; Sternke-Hoffmann, R.; Peduzzo, A.; Ziaunys, M.; Buell, A.K.; Smirnovas, V. The Environment Is a Key Factor in Determining the Anti-Amyloid Efficacy of EGCG. Biomolecules 2019, 9, 855. https://doi.org/10.3390/biom9120855

AMA Style

Sneideris T, Sakalauskas A, Sternke-Hoffmann R, Peduzzo A, Ziaunys M, Buell AK, Smirnovas V. The Environment Is a Key Factor in Determining the Anti-Amyloid Efficacy of EGCG. Biomolecules. 2019; 9(12):855. https://doi.org/10.3390/biom9120855

Chicago/Turabian Style

Sneideris, Tomas; Sakalauskas, Andrius; Sternke-Hoffmann, Rebecca; Peduzzo, Alessia; Ziaunys, Mantas; Buell, Alexander K.; Smirnovas, Vytautas. 2019. "The Environment Is a Key Factor in Determining the Anti-Amyloid Efficacy of EGCG" Biomolecules 9, no. 12: 855. https://doi.org/10.3390/biom9120855

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