Curcumin Inhibits the Primary Nucleation of Amyloid-Beta Peptide: A Molecular Dynamics Study

The amyloid plaques are a key hallmark of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Amyloidogenesis is a complex long-lasting multiphase process starting with the formation of nuclei of amyloid peptides: a process assigned as a primary nucleation. Curcumin (CU) is a well-known inhibitor of the aggregation of amyloid-beta (A beta) peptides. Even more, CU is able to disintegrate preformed A beta firbils and amyloid plaques. Here, we simulate by molecular dynamics the primary nucleation process of 12 A beta peptides and investigate the effects of CU on the process. We found that CU molecules intercalate among the A beta chains and bind tightly to them by hydrogen bonds, hydrophobic, pi-pi, and cation-pi interactions. In the presence of CU, the A beta peptides form a primary nucleus of a bigger size. The peptide chains in the nucleus become less flexible and more disordered, and the number of non-native contacts and hydrogen bonds between them decreases. For comparison, the effects of the weaker A beta inhibitor ferulic acid (FA) on the primary nucleation are also examined. Our study is in good agreement with the observation that taken regularly, CU is able to prevent or at least delay the onset of neurodegenerative disorders.