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5 September 2019

Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease

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Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow 226026, India
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Department of Pharmacy, Abdul Wali Khan University Mardan 23200, Pakistan
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Department of Pharmaceutics, College of Pharmacy, University of Hail, PO Box 2440, Ha’il – 81451, Saudi Arabia
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Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box: 2457, Riyadh 11451, Saudi Arabia
This article belongs to the Special Issue Natural Products in Alzheimer’s Disease Drug Discovery

Abstract

Alzheimer’s disease (AD) is a widespread dynamic neurodegenerative malady. Its etiology is still not clear. One of the foremost pathological features is the extracellular deposits of Amyloid-beta (Aβ) peptides in senile plaques. The interaction of Aβ and the receptor for advanced glycation end products at the blood-brain barrier is also observed in AD, which not only causes the neurovascular anxiety and articulation of proinflammatory cytokines, but also directs reduction of cerebral bloodstream by upgrading the emission of endothelin-1 to induce vasoconstriction. In this process, RAGE is deemed responsible for the influx of Aβ into the brain through BBB. In the current study, we predicted the interaction potential of the natural compounds vincamine, ajmalicine and emetine with the Aβ peptide concerned in the treatment of AD against the standard control, curcumin, to validate the Aβ peptide–compounds results. Protein-protein interaction studies have also been carried out to see their potential to inhibit the binding process of Aβ and RAGE. Moreover, the current study verifies that ligands are more capable inhibitors of a selected target compared to positive control with reference to ΔG values. The inhibition of Aβ and its interaction with RAGE may be valuable in proposing the next round of lead compounds for effective Alzheimer’s disease treatment.

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