Author(s)

Michio Hashimoto^1*, Shahdat Hossain^1,2, Kentaro Matsuzaki¹, Abdullah Al Mamun¹, Hiroyuki Arai³, Osamu Shido¹

¹Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumoshi, Japan.
²Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Dhaka, Bangladesh.
³Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.

The accumulation of amyloid β peptide_1-42 (Aβ_1-42) 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 Aβ_1-42 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 Aβ_1-42 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 Aβ_1-42. Computational analyses of the binding of DHA to Aβ_1-42, as evaluated by docking studies, further corroborated the inhibitory effect of DHA on in vitro Aβ_1-42 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.

Docosahexaenoic Acid, Alzheimer’s Disease, Amyloid Beta Peptide, Molecular Docking, In Silico, Drug Design, Protein Data Bank

Hashimoto, M. , Hossain, S. , Matsuzaki, K. , Mamun, A. , Arai, H. and Shido, O. (2016) Computational Analyses of Docosahexaenoic Acid (DHA, C22:6, n-3) with Alzheimer’s Disease-Causing Amyloid Peptide Aβ_1-42 Reassures Its Therapeutic Utility. Advances in Alzheimer's Disease, 5, 73-86. doi: 10.4236/aad.2016.52006.