LAUSR

Amyloidogenic protein/peptide aggregation into fibrillar aggregates is associated with multiple amyloidoses, including widespread neurodegenerative disorders. Despite years of research and a well-understood mechanism, there are still very few treatments available for the increasing number of amyloid-related disorders. In recent years, the search for potential anti-aggregation compounds has shifted toward naturally occurring molecules, with one of the most promising being epigallocatechin-3-gallate (EGCG). This polyphenolic compound was shown to inhibit the aggregation of several amyloidogenic proteins/peptides, including amyloid-beta (related to Alzheimer’s disease) and alpha-synuclein (related to Parkinson’s disease). However, multiple reports have indicated its limited stability under physiological conditions and the possibility of EGCG autoxidation products being the actual inhibitory compounds. In this work, we explore how different EGCG autoxidation products associate with non-aggregated insulin, as well as how they affect its aggregation and resulting fibril structure. We also show that there is a specific incubation time required for the emergence of compounds, which alters the amyloid aggregation process.