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

Tomas Sneideris, Andrius Sakalauskas, Rebecca Sternke-Hoffmann, Alessia Peduzzo, Mantas Ziaunys, Alexander Kai Büll*, Vytautas Smirnovas

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.
Original languageEnglish
Article number855
JournalBiomolecules
Volume9
Issue number12
Number of pages17
ISSN2218-273X
DOIs
Publication statusPublished - 2019

Keywords

  • Insulin
  • α-synuclein
  • Inhibition
  • EGCG
  • Amyloid aggregation

Cite this

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