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

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 produ...

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Autores principales: Ahmad, Syed Sayeed, Khan, Haroon, Danish Rizvi, Syed Mohd., Ansari, Siddique Akber, Ullah, Riaz, Rastrelli, Luca, Mahmood, Hafiz Majid, Siddiqui, Mohd. Haris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767296/
https://www.ncbi.nlm.nih.gov/pubmed/31491967
http://dx.doi.org/10.3390/molecules24183233
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author Ahmad, Syed Sayeed
Khan, Haroon
Danish Rizvi, Syed Mohd.
Ansari, Siddique Akber
Ullah, Riaz
Rastrelli, Luca
Mahmood, Hafiz Majid
Siddiqui, Mohd. Haris
author_facet Ahmad, Syed Sayeed
Khan, Haroon
Danish Rizvi, Syed Mohd.
Ansari, Siddique Akber
Ullah, Riaz
Rastrelli, Luca
Mahmood, Hafiz Majid
Siddiqui, Mohd. Haris
author_sort Ahmad, Syed Sayeed
collection PubMed
description 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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spelling pubmed-67672962019-10-02 Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease Ahmad, Syed Sayeed Khan, Haroon Danish Rizvi, Syed Mohd. Ansari, Siddique Akber Ullah, Riaz Rastrelli, Luca Mahmood, Hafiz Majid Siddiqui, Mohd. Haris Molecules Article 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. MDPI 2019-09-05 /pmc/articles/PMC6767296/ /pubmed/31491967 http://dx.doi.org/10.3390/molecules24183233 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahmad, Syed Sayeed
Khan, Haroon
Danish Rizvi, Syed Mohd.
Ansari, Siddique Akber
Ullah, Riaz
Rastrelli, Luca
Mahmood, Hafiz Majid
Siddiqui, Mohd. Haris
Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease
title Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease
title_full Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease
title_fullStr Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease
title_full_unstemmed Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease
title_short Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease
title_sort computational study of natural compounds for the clearance of amyloid-βeta: a potential therapeutic management strategy for alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767296/
https://www.ncbi.nlm.nih.gov/pubmed/31491967
http://dx.doi.org/10.3390/molecules24183233
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