Mechanisms of amyloid inhibition remains poorly understood, in part because most protein targets of amyloid assembly are either partially unfolded or intrinsically disordered, which hinders detailed structural characterizations of protein-inhibitor complexes and structural-based mechanistic elucidation. Herein we employed a small molecule screening approach to identify inhibitors against three prototype amyloidogenic proteins: amylin, Aβ and tau. One remarkable class of inhibitors identified was catechol-containing compounds and redox-related quinones/ anthraquinones. Further mechanistic studies determined that the redox state of the broad class of catechol-containing inhibitors is a key determinant of the amyloid inhibitor activities.

中文翻译：

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含儿茶酚的化合物是一类广泛的淀粉样蛋白抑制剂：氧化还原状态是​​抑制活性的关键决定因素

淀粉样蛋白抑制的机制仍知之甚少，部分原因是大多数淀粉样蛋白组装体的蛋白质靶标要么部分展开，要么固有地无序，这阻碍了蛋白质抑制剂复合物的详细结构表征和基于结构的机理阐明。在本文中，我们采用小分子筛选方法来鉴定针对三种原型淀粉样蛋白的抑制剂：淀粉样蛋白，Aβ和tau。鉴定出的一类杰出的抑制剂是含儿茶酚的化合物和氧化还原相关的醌/蒽醌。进一步的机理研究确定，广泛类别的含儿茶酚的抑制剂的氧化还原状态是​​淀粉样蛋白抑制剂活性的关键决定因素。