Modulation of beta-amyloid aggregation using ascorbic acid

Studies have shown that the level of ascorbic acid (AA) is reduced in the brain of Alzheimer's disease (AD) patients. However, its effect on amyloid-beta 1-42 (A beta(42)) aggregation has not yet been elucidated. Here we investigated for the first time the effect of AA on A beta(42) aggregation using fluorescence assay, circular dichroism, atomic force microscopy, isothermal titration calorimetry, ligand docking, and molecular dynamics. Our results showed that the fibril content decreases in the growth phase when the peptides are co-incubated with AA. AA molecules bind to A beta(42) peptides with high binding affinity and a binding site for AA between the beta-strands of A beta(42) oligomers prevents the stack of adjacent strands. We demonstrate the inhibitory effect of AA on the aggregation of A beta(42) and its molecular interactions, which can contribute to the development of an accessible therapy for AD and also to the design of novel drugs for other amyloidogenic diseases. (C) 2022 Published by Elsevier B.V.