beta-Amyloid Amorphous Aggregates Induced by the Small Natural Molecule Ferulic Acid

There is an emerging interest in small natural molecules for their potential therapeutic use in neurodegenerative disorders like Alzheimer's disease (AD). Ferulic acid (FA), an antioxidant phenolic compound present in fruit and vegetables, has been proposed as an inhibitor of beta amyloid (A?) pathological aggregation. Using fluorescence and Fourier transform infrared spectroscopy, electrophoresis techniques, chromatographic analysis, and confocal microscopy, we investigated the effects of FA in the early stages of A? fibrillogenesis in vitro. Our results show that FA interacts promptly with A? monomers/oligomers, interfering since the beginning with its self-assembly and finally forming amorphous aggregates more prone to destabilization. These findings highlight the molecular basis underlying FA antiamyloidogenic activity in AD.