Mechanistic insights of curcumin interactions with the core-recognition motif of β-amyloid peptide.

Alzheimer's disease is a neurodegenerative disease affecting millions of people worldwide. The proteolytic cleavage of amyloid precursor protein forms amyloid beta peptide (Aβ(1-42)), which aggregates to form senile plaques. The KLVFF motif present in Aβ(1-42) is essential for aggregation. Curcumin, a prinicipal curcuminoid present in turmeric, shows therapeutic activity against Alzheimer's disease. However, the nature of interaction between the A(β1-42) peptide and curcumin remains unexplored. Studies on the interaction of the core-recognition motif KLVFF with curcumin can be extrapolated to decipher the interactions between A(β1-42) and curcumin. Our data show that curcumin and KLVFF interact strongly through hydrophobic forces and are stabilized by hydrogen bonding. The hydrophobic interactions were confirmed from the positive shift in the phase transition temperature. Fluorescence quenching studies demonstrate a static quenching mechanism. FTIR data confirm the β sheet breaking ability of curcumin, which is also substantiated by cell culture studies.