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 巻 2 号 73-86 頁 2016-6-29 発行
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タイトル
Computational analyses of docosahexaenoic acid (DHA, C22:6, n-3) with Alzheimer’s disease-causing amyloid peptide Aβ1–42 reassures its therapeutic utility.
著者
Shahdat Hossain
Abdullah Al Mamun
Arai Hiroyuki
収録物名
Advances in Alzheimer’s Disease
5
2
開始ページ 73
終了ページ 86
収録物識別子
ISSN 2169-2459
EISSN 2169-2467
内容記述
その他
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.
主題
Docosahexaenoic Acid
Alzheimer’s Disease
Amyloid Beta Peptide
Molecular Docking
In Silico
Drug Design
Protein Data Bank
言語
英語
資源タイプ 学術雑誌論文
出版者
Scientific Research Publishing (SCIRP)
発行日 2016-6-29
出版タイプ Version of Record(出版社版。早期公開を含む)
アクセス権 オープンアクセス
関連情報
[DOI] 10.4236/aad.2016.52006