Molecular interactions of resveratrol with Aβ 42 peptide and fibril during in-vitro Aβ 42 aggregation

Amyloid aggregates are responsible for the development of oxidative stress and neurotoxicity in the brain. Several amino acid residues of amyloid beta (Aβ) 42 establish different molecular interactions to form and stabilize these aggregates, which can be targeted to prevent the aggregation. Resveratrol (Res) has inhibitory properties against Aβ 42 aggregation but studies elucidating its interactions with different residues of Aβ 42 aggregates are scarce. In the present study, we have discerned the molecular interactions of Res with different amino acid residues of Aβ 42 peptide and fibril during in-vitro Aβ 42 aggregation. Inhibitory properties of Res against amyloid aggregation were established through ANS and Thioflavin-T fluorescence assay, congo red assay and CD spectroscopy. The molecular interactions were established through molecular docking and 100 ns molecular dynamics simulations. The hydrophobic regions of Aβ 42 peptide, responsible for the formation of aggregates, were better protected in the presence of Res as indicated by ANS assay. Th-T and congo red assay suggested that Res prevented the formation of cross β-sheet structures. CD spectra analysis revealed that in the presence of Res, the secondary structure content was significantly decreased. MD simulation analysis revealed that Res formed strong molecular interactions with hydrophobic and secondary structure forming amino acid residues, which are involved in the amyloid aggregation and stabilization of aggregates. In conclusion, these interactions might have led to the decline in secondary structure content, formation of unordered nontoxic aggregates and prevention of the formation of sufuranyl free radical.