Neuraminidase as a novel therapeutic management strategy for Alzheimer's disease: evidenced through molecular docking, molecular dynamic simulation and gene expression analysis.
Sami I Alzarea, Omar Awad Alsaidan, Hassan H Alhassan, Abdulaziz Ibrahim Alzarea, Tariq G Alsahli, Metab Alharbi, Muhammad Afzal, Mohammad Jaffar Sadiq Mantargi
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引用次数: 0
Abstract
Introduction: Neuraminidase in humans is studied to see how well repurposed oseltamivir works for treating Alzheimer's disease (AD) using methods like molecular docking, molecular dynamic (MD) simulation, and gene expression analysis. Gene enrichment analysis was also studied to understand the behaviour of neuraminidases in humans.
Methods: Molecular docking was done using oseltamivir and the neuraminidase proteins with the PyRx tool, and the results were analysed using BIOVIA Discovery Studio. MD simulation (50 ns) of the oseltamivir and neuraminidase complex was performed using GROMACS tools. The gene expression analysis and gene enrichment study were done using GEO2R, which showed the results as log FC and significant values. Enricher tool-based gene enrichment analysis was done to determine the gene behaviour related to the AD.
Results: The molecular docking showed a strong connection between oseltamivir and neuraminidase (-6.5 kcal/mol), acetylcholinesterase (-7.9 kcal/mol), CDKs (-6.5 kcal/mol), and GSKs (-6.6 kcal/mol), interacting with different amino acids in the protein sequences. MD simulations showed a strong interaction between the ligand and neuraminidase, with stable measurements indicating that both the protein and ligand remained consistent in size and energy, which is better explained through the results of MM_PBSA and MM_GBSA analysis of the complex, resulting in the ΔE_vdW, ΔE_elec, ΔG_polar, ΔG_nonpolar, ΔG_gas, (ΔE_vdW + ΔEEL), ΔG_solvation: (ΔG_polar + ΔG_nonpolar) and ΔG_bind: total energies suggesting the complex stayed stable in conditions similar to those resembling natural cell. The gene expression analysis expressed TUBB3 (formation of beta-tubulin), FABP3 (regulates alpha-synuclein uptake in dopaminergic neurons), and CALM1 (calcium signal transduction pathway) to be highly upregulated in the given conditions with kinase binding (p = 0.0006541) and protein phosphatase regulatory activity (p = 0.001357) were highly upregulated, implicating their importance in the AD.
Discussion: The study ends on a hopeful note for using oseltamivir to treat neurological diseases, but it suggests that future research should include a solid cell line study, an in vitro study, and a clinical study.
期刊介绍：
Frontiers in Chemistry is a high visiblity and quality journal, publishing rigorously peer-reviewed research across the chemical sciences. Field Chief Editor Steve Suib at the University of Connecticut is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to academics, industry leaders and the public worldwide.
Chemistry is a branch of science that is linked to all other main fields of research. The omnipresence of Chemistry is apparent in our everyday lives from the electronic devices that we all use to communicate, to foods we eat, to our health and well-being, to the different forms of energy that we use. While there are many subtopics and specialties of Chemistry, the fundamental link in all these areas is how atoms, ions, and molecules come together and come apart in what some have come to call the “dance of life”.
All specialty sections of Frontiers in Chemistry are open-access with the goal of publishing outstanding research publications, review articles, commentaries, and ideas about various aspects of Chemistry. The past forms of publication often have specific subdisciplines, most commonly of analytical, inorganic, organic and physical chemistries, but these days those lines and boxes are quite blurry and the silos of those disciplines appear to be eroding. Chemistry is important to both fundamental and applied areas of research and manufacturing, and indeed the outlines of academic versus industrial research are also often artificial. Collaborative research across all specialty areas of Chemistry is highly encouraged and supported as we move forward. These are exciting times and the field of Chemistry is an important and significant contributor to our collective knowledge.
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