Real-time BODIPY-binding assay to screen inhibitors of the early oligomerization process of A β 1-42 peptide.

Real-time BODIPY-binding assay to screen inhibitors of the early oligomerization process of Aβ 1-42 peptide. Chembiochem. 2019 Nov 08;: Authors: Tonali N, Dodero VI, Kaffy J, Hericks L, Ongeri S, Sewald N Abstract Misfolding and aggregation of amyloid-β 1-42 peptide (Aβ1-42) play a central role in the pathogenesis of Alzheimer's disease (AD). Targeting the highly cytotoxic oligomeric species formed during the early stages of the aggregation process represents a promising therapeutic strategy to reduce the toxicity associated with Aβ1-42. Currently, the Thioflavin T (ThT) assay is the only established spectrofluorometric method to screen aggregation inhibitors. The success of the ThT assay is that it can detect Aβ1-42 aggregates with high β-sheet content, such as protofibrils or fibrils, which appear in the late aggregation steps. Unfortunately, by ThT assay the detection of inhibitors of the early soluble oligomers presenting a low β-sheet character is challenging. Herein, we report a new, facile, and robust BODIPY real-time assay suitable for 96-well plate format that allows screening of compounds as selective inhibitors of the formation of Aβ1-42 oligomers. These inhibitors decrease the cellular toxicity of Aβ1-42 while they failed in the ThT assay. Our findings have been confirmed and validated by structural analysis and cell viability assays under comparable experimental conditions. We demonstrate that the BODIPY assay i...
Source: Chembiochem - Category: Biochemistry Authors: Tags: Chembiochem Source Type: research