Catechol-Containing Compounds are a Broad Class of Amyloid Inhibitors: I. Redox State is a Key Determinant of the Activities of the Inhibitory Activities

Abstract

Mechanisms of amyloid inhibition remains poorly understood, in part because most protein targets of amyloid assembly are partially unfolded or intrinsically disordered, which hinders detailed structural characterization 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, A{beta} 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 compounds is a key determinant of the amyloid inhibitor activities.