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.

中文翻译：

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探索 Epigallocatechin-3-Gallate 自氧化产物：抗淀粉样蛋白特性出现所需的特定孵育时间

淀粉样蛋白/肽聚集成纤维状聚集体与多种淀粉样变性有关，包括广泛的神经退行性疾病。尽管经过多年的研究和充分了解的机制，对于越来越多的淀粉样蛋白相关疾病，仍然很少有可用的治疗方法。近年来，寻找潜在的抗聚集化合物已转向天然存在的分子，其中最有希望的分子之一是表没食子儿茶素-3-没食子酸酯 (EGCG)。这种多酚化合物被证明可以抑制几种淀粉样蛋白/肽的聚集，包括β-淀粉样蛋白（与阿尔茨海默病相关）和 α-突触核蛋白（与帕金森病相关）。然而，多项报告表明其在生理条件下的稳定性有限，并且 EGCG 自氧化产物可能是实际的抑制化合物。在这项工作中，我们探讨了不同的 EGCG 自氧化产物如何与非聚集胰岛素相关联，以及它们如何影响其聚集和由此产生的原纤维结构。我们还表明，化合物的出现需要特定的孵育时间，这会改变淀粉样蛋白的聚集过程。