Destabilizing Alzheimer's Aβ42 protofibrils with oleocanthal: In-silico approach

Alzheimer's disease (AD) is correlated with the formation of toxic fibril aggregates from amyloid- (Aβ) peptides. Finding effective inhibitors of Aβ aggregation is a critical step in the development of medications to treat Alzheimer's disease. Recent research found that oleocanthal, a chemical derived from Olive oil efficiently reduce Aβ cytotoxicity. The influence of oleocanthal molecules on preformed A β fibrils, as well as the atomic-level specifics of interactions between oleocanthal and A β fibrils, are, however, largely unexplored. In this study, molecular dynamics (MD) simulations was performed for 100ns on Aβ 17–42 protofibril with and without oleocanthal molecules. It was observed that oleocanthal molecules mostly bind to central hydrophobic core (CHC) and cavity of protofibril. The binding of oleocanthal with C-terminal hydrophobic groove has minor effect on the architectures of A β 17–42 protofibrils, whereas binding to the outer CHC and cavity severely destabilises Aβ protofibril stability. The protofibril were primarily disrupted by disrupting the Asp23-Lys28 salt bridges and the inter-peptide β = sheet in β1 region. Itwas also investigated that how the oleocanthal molecules enter the cavity of Aβ17–42 protofibril.Numerous MD simulations were processed to find out the influence of oleocanthal molecules on U-shaped A β 42 protofibril. Our simulations revealed that by binding to the protofibril cavity, oleocanthal molecules can destabilise U-shaped Aβ protofibril. Present study reveals the method through which oleocanthal molecules inhibit the aggregation of A β protofibril, which could lead to the creation of new medication options for the treatment of Alzheimer's disease.