Detergent-like Interaction of Congo Red with the Amyloid β Peptide

Abstract

Accumulating evidence links prefibrillar oligomeric species of the amyloid beta peptide (Abeta) to cellular toxicity in Alzheimer's disease, potentially via disruption of biological membranes. Congo red (CR) affects protein aggregation. It is known to self-associate into micelle-like assemblies but still reduces the toxicity of Abeta aggregates in cell cultures and model organisms. We show here that CR interacts with Abeta(1-40) in a manner similar to that of anionic detergents. Although CR promotes beta sheet formation and peptide aggregation, it may also solubilize toxic protein species, making them less harmful to critical cellular components and thereby reducing amyloid toxicity.

Congo red modulates ACh-induced Ca2+ oscillations in single pancreatic acinar cells of mice

“…This feature, in addition to its small molecular size and ease of penetration of the blood-brain barrier, make congo red useful as a molecular probe for both the antemortem and in vivo visualization and quantification of brain amyloid [1,2,5,6] . Interestingly, emerging studies demon- [4,9] . It has been reported that congo red is able to block Aβ aggregation and toxicity in rat hippocampal neuron culture [20] , HeLa and PC12 cells and in human macrophage culture [21,22] .…”

“…Congo red is a secondary diazo dye that is usually used as an indicator for the presence of amyloid fibrils and is one of the model compounds that has been extensively studied for its interaction with amyloid beta peptide (Aβ) [1][2][3][4][5] . In addition, it has been found that congo red can block Aβ-formed ion channels [6,7] .…”

Supramolecular Systems as Protein Ligands

“…In addition to the degree of packing and the protein's intrinsic stability it also depends -as remarked above -upon function-related conformational rearrangement [35,36,38,39].…”

“…In some cases, however, even a tightly packed protein may -when binding its natural target ligand -undergo sufficient structural rearrangement to permit penetration of additional large supramolecular ligands penetrating outside of the primary binding site. This type of interaction, while temporary, often drastically modifies the function of the protein [35,36].…”

Metal Ions Introduced to Proteins by Supramolecular Ligands

“…The complexation of CR with amyloids is the subject of numerous studies [29][30][31]. The problem is difficult and its molecular underpinnings remain speculative, since CR itself is not visualized under electron microscopy, while amyloids -despite their ordered structure -do not attain the necessary level of crystallization order.…”