کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6920508 | 1447922 | 2018 | 36 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Across the blood-brain barrier: Neurotherapeutic screening and characterization of naringenin as a novel CRMP-2 inhibitor in the treatment of Alzheimer's disease using bioinformatics and computational tools
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی کامپیوتر
نرم افزارهای علوم کامپیوتر
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چکیده انگلیسی
The discovery and developmental processes of CNS drugs have been limited by the inability of potential drug molecules to pass through the blood-brain barrier (BBB). This presents a significant setback in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD), hence the need for compounds that can adhere strictly to the selective criteria of suitable CNS drugs. Collapsin response mediator protein-2 (CRMP-2) has been recently identified as a viable target in neurotherapeutics due to its involvement in the etiology of AD. As shown in previous studies, Naringenin (NAR), a small molecule derivative of Drynaria rhizome (DR) extract, specifically binds CRMP-2 and reduces its phosphorylation. This was shown to facilitate axonal regrowth, with improvement in cognition and learning. Herein, we report the first account of the use of cheminformatics techniques to define the CNS drug-suitability of NAR using selective criteria, coupled with the prediction of possible biological activities and toxicities. Also, we evaluated the mechanistic activity of NAR by modeling its molecular interaction with human CRMP-2 (hCRMP-2). Physicochemical analyses revealed the suitability of NAR as a CNS drug and its ability to transverse the BBB. Possible neurogenic, anti-carcinogenic and cardioprotective activities were also predicted. NAR exhibited favorable binding to CRMP-2 and formed strong bonds with active site residues, which accounts for its stabilization and affinity. Moreover, NAR induced notable conformational changes in CRMP-2, an occurrence that could possibly disrupt kinase-mediated phosphorylation. These findings will aid in the optimization of NAR and improve its neurotherapeutic activities in the treatment of AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Computers in Biology and Medicine - Volume 98, 1 July 2018, Pages 168-177
Journal: Computers in Biology and Medicine - Volume 98, 1 July 2018, Pages 168-177
نویسندگان
Maryam Lawal, Fisayo A. Olotu, Mahmoud E.S. Soliman,