Computational Analyses of Docosahexaenoic Acid DHA, C22:6, n-3 with Alzheimer’s Disease-Causing Amyloid Peptide Aβ1-42 Reassures Its Therapeutic UtilityReportar como inadecuado




Computational Analyses of Docosahexaenoic Acid DHA, C22:6, n-3 with Alzheimer’s Disease-Causing Amyloid Peptide Aβ1-42 Reassures Its Therapeutic Utility - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.

KEYWORDS

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

Cite this paper

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 Aβ1-42 Reassures Its Therapeutic Utility. Advances in Alzheimer-s Disease, 5, 73-86. doi: 10.4236-aad.2016.52006.





Autor: Michio Hashimoto1*, Shahdat Hossain1,2, Kentaro Matsuzaki1, Abdullah Al Mamun1, Hiroyuki Arai3, Osamu Shido1

Fuente: http://www.scirp.org/



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