Promotion and Inhibition of Amyloid-β Peptide Aggregation: Molecular Dynamics Studies

Aggregates of amyloid-beta (A beta) peptides are known to be related to Alzheimer's disease. Their aggregation is enhanced at hydrophilic-hydrophobic interfaces, such as a cell membrane surface and air-water interface, and is inhibited by polyphenols, such as myricetin and rosmarinic acid. We review molecular dynamics (MD) simulation approaches of a full-length A beta peptide, A beta 40, and A beta(16-22) fragments in these environments. Since these peptides have both hydrophilic and hydrophobic amino acid residues, they tend to exist at the interfaces. The high concentration of the peptides accelerates the aggregation there. In addition, A beta 40 forms a beta-hairpin structure, and this structure accelerates the aggregation. We also describe the inhibition mechanism of the A beta(16-22) aggregation by polyphenols. The aggregation of A beta(16-22) fragments is caused mainly by the electrostatic attraction between charged amino acid residues known as Lys16 and Glu22. Since polyphenols form hydrogen bonds between their hydroxy and carboxyl groups and these charged amino acid residues, they inhibit the aggregation.

Automated summary

Aggregates of amyloid-beta (Aβ) peptides are enhanced at hydrophilic-hydrophobic interfaces and inhibited by polyphenols. Aβ40 accelerates aggregation due to its beta-hairpin structure, while polyphenols inhibit Aβ(16-22) aggregation by forming hydrogen bonds.