Computational analyses of docosahexaenoic acid (DHA, C22:6, n-3) with Alzheimer’s disease-causing amyloid peptide Aβ1–42 reassures its therapeutic utility.

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The accumulation of amyloid β peptide1-42 (Aβ1-42) masses in the brains of Alzheimer’s Disease (AD) patients is associated with neuronal loss and memory deficits. We have previously reported that oral administration of docosahexaenoic acid (DHA, C22:6, n-3) significantly decreases Aβ burden in the brains of AD model rats and that direct in vitro incubation of DHA with Aβ1-42 curbs the progression of amyloid fibrillation. In the present in silico study, we investigated whether DHA computationally binds with amyloid peptides. The NMR solution structures of Aβ1-42 were downloaded from the Protein Data Bank (PDB IDs: 1Z0Q and 2BEG). The binding of DHA to Aβ peptides was assessed by molecular docking using both a flexible and rigid docking system. Thioflavin T (ThT) was used as positive control. The chemical structures of ThT and DHA were modeled and converted to the PDB format using PRODRUG. Drug-like properties of DHA were evaluated by ADME (Absorption, Distribution, Metabolism, and Excretion). DHA was found to successfully dock with Aβ1-42. Computational analyses of the binding of DHA to Aβ1-42, as evaluated by docking studies, further corroborated the inhibitory effect of DHA on in vitro Aβ1-42 fibrillogenesis and might explain the in vivo reduction of amyloid burden observed in the brains of DHA-administered AD model rats demonstrated in our previous study. These computational data suggest the potential utility of DHA as a preventive medication in Aβ-induced neurodegenerative diseases, including AD.