The effects of ferulic acid on β-amyloid fibrillar structures investigated through experimental and computational techniques

BackgroundCurrent research has indicated that small natural compounds could interfere with β-amyloid fibril growth and have the ability to disassemble preformed folded structures. Ferulic acid (FA), which possesses both hydrophilic and hydrophobic moieties and binds to peptides/proteins, is a potential candidate against amyloidogenesis. The molecular mechanisms connected to this action have not been elucidated in detail yet.MethodsHere the effects of FA on preformed fibrils are investigated by means of a concerted experimental–computational approach. Spectroscopic techniques, such as FTIR, fluorescence, size exclusion chromatography and confocal microscopy in combination with molecular dynamics simulations are used to identify those features which play a key role in the destabilization of the aggregates.ResultsExperimental findings highlight that FA has disruptive effects on the fibrils. The computational analysis suggests that dissociation of peptides from the amyloid superstructures could take place along the fibril axis and be primarily determined by the cooperative rupture of the backbone hydrogen bonds and of the Asp-Lys salt bridges.ConclusionFA clusters could induce a sort of stabilization and tightening of the fibril structure in the short term and its disruption in the long term, inhibiting further fibril re-assembly through FA screening effects.General significanceThe combination of experimental and computational techniques could be successfully used to identify the disrupting action of FA on preformed Aβ fibrils in water solution.

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► Ferulic acid (FA) covers the Aβ fibrillar structures and inserts between the oligopeptide chains.
► FA could interact with Asp23-Lys28 salt bridges disrupting the Asp-Lys arrangement.
► FA causes fibril solvation, unpacking of the chains, and Aβ fibril disruption.
► FA–fibril interaction could inhibit Aβ peptide re-association.