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

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.

• Authors: Syed Sayeed Ahmad, Haroon Khan, Syed Mohd Danish Rizvi, Siddique Akber Ansari, Riaz Ullah, Luca Rastrelli, Hafiz Majid Mahmood, Mohd Haris Siddiqui
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 24 Issue 18 (Sep 05 2019) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 31491967 (Publication Type: Journal Article)

Chemical References

• Amino Acids
• Amyloid beta-Peptides
• Amyloidogenic Proteins
• Biological Products
• Ligands

Topics

• Alzheimer Disease
• Amino Acids
• Amyloid beta-Peptides (antagonists & inhibitors, chemistry, metabolism)
• Amyloidogenic Proteins (antagonists & inhibitors, chemistry)
• Binding Sites
• Biological Products (chemistry, pharmacology)
• Humans
• Hydrogen Bonding
• Ligands
• Models, Molecular
• Molecular Conformation
• Molecular Docking Simulation
• Molecular Dynamics Simulation
• Protein Binding
• Structure-Activity Relationship