Characterization of Aβ aggregation mechanism probed by congo red

beta-Amyloid peptide (A beta) aggregates are toxic to neuron and the main cause of Alzheimer's disease (AD). The role of congo red (CR) on A beta aggregation is controversial in aqueous solution. Both prevention and promotion of A beta aggregation have been proposed, suggesting that CR may interact with A beta of different structural conformations resulting in different effects on A beta aggregation behavior. CR with these characteristics can be applied to probe the molecular mechanism of A beta aggregation. Therefore, in the present study, we used CR as a probe to study the A beta aggregation behavior in sodium dodecyl sulfate (SDS) condition. Our results show that A beta(40) adopts two short helices at Q15-S26 and K28-L34 in the SDS environment. CR can interact with the helical form of A beta(40), and the main interaction site is located at the first helical and hydrophobic core region, residues 17-25, which is assigned as a discordant helix region. Furthermore, CR may prevent A beta(40) undergoing alpha-helix to beta-strand conversion, and therefore aggregation through stabilizing the helical conformation of discordant helix in SDS environment, suggesting that the discordant helix plays a key role on the conformational stabilization of A beta. Our present study implies that any factors or molecules that can stabilize the discordant helical conformation may also prevent the A beta aggregation in membrane associated state. This leads to a new therapeutic strategy for the development of lead compounds to AD.