Interplay between epigallocatechin-3-gallate and ionic strength during amyloid aggregation

PeerJ. 2021 Oct 22:9:e12381. doi: 10.7717/peerj.12381. eCollection 2021.


The formation and accumulation of protein amyloid aggregates is linked with multiple amyloidoses, including neurodegenerative Alzheimer's or Parkinson's disease. The mechanism of such fibril formation is impacted by various environmental conditions, which greatly complicates the search for potential anti-amyloid compounds. One of these factors is solution ionic strength, which varies between different aggregation protocols during in vitro drug screenings. In this work, we examine the interplay between ionic strength and a well-known protein aggregation inhibitor-epigallocatechin-3-gallate. We show that changes in solution ionic strength have a major impact on the compound's inhibitory effect, reflected in both aggregation times and final fibril structure. We also observe that this effect is unique to different amyloid-forming proteins, such as insulin, alpha-synuclein and amyloid-beta.

Keywords: Aggregation inhibition; Alpha-synuclein; Amyloid beta; Amyloids; EGCG; Insulin; Ionic strength; Protein aggregation.

Grants and funding

This research was funded by the grant no. S-SEN-20-3 from the Research Council of Lithuania. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.