A hallmark of Alzheimer's disease is deposition of insoluble amyloid-beta (Abeta) fibrils in the brain. Due to unusually high stability of amyloid fibrils with cross-stacked beta-sheet structure, conversion of oligomers/protofibrils to fibrils is often considered as an irreversible process. Recently, we discovered that two biocompatible, blood-brain barrier permeable molecules (brilliant blue G and erythrosine B) can modulate Abeta aggregation and cytotoxicity. Combined with another Abeta aggregation modulator (methylene blue), we explored whether these molecules can reverse the fibril formation process. Our preliminary results indicate that all three molecules lead to substantial secondary structure change and/or disintegration of Abeta40 fibrils. We plan to explore thermodynamic features of amyloid fibrils and small-molecule induced conformers and determine factors critical to reverse the amyloid fibrillization process.

Secondary structure changes and disintegration of amyloid-beta fibrils mediated by biocompatible, blood-brain barrier permeable small molecules

243rd National Meeting (2012)

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