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ORIGINAL RESEARCH ARTICLE

Key regulators of Alzheimer’s disease: Network biology and in silico analysis with acetylcholinesterase and glutamate inhibitors

Sayantan Das1*
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1 Department of Life Science, Faculty of Biological Sciences, University of Essex, Colchester, Essex, United Kingdom
GPD, 026050003 https://doi.org/10.36922/GPD026050003
Received: 28 January 2026 | Revised: 4 March 2026 | Accepted: 18 March 2026 | Published online: 30 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Alzheimer’s disease (AD) is a complex, progressive neurodegenerative disorder driven by both genetic and environmental factors, with hallmark features including amyloid-β plaques and neurofibrillary tangles. Despite substantial research, the majority of currently licensed medications are still symptomatic, highlighting the need for multi-target and network-based treatment approaches. This study employed a systems biology approach to identify important regulatory proteins implicated in AD development and to assess their interaction patterns with approved glutamate and cholinesterase inhibitors. A protein–protein interaction network was developed using the 85 overlapping genes identified when AD-associated genes were selected from six significant biomedical databases. Seven major regulators were identified using centrality and hub analyses, including APP, APOE, BDNF, VEGFA, PSEN1, CASP1, and NOTCH1. Their participation in axon formation, signal transduction, neuroinflammatory processes, and neurodegenerative pathways was revealed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The binding affinities of donepezil, galantamine, rivastigmine, and memantine toward these targets were evaluated by molecular docking using AutoDock Vina. While APP demonstrated relatively weaker affinities, BDNF demonstrated the strongest overall binding interactions, especially with donepezil. Memantine showed significant binding to PSEN1, indicating that amyloidogenic processes may be indirectly modulated. These results demonstrate the usefulness of integrated computational techniques in identifying new therapeutic interaction networks and support a multi-target pharmacological paradigm. This study offers a systems-level basis for medication repurposing and precision intervention strategies in AD, although additional experimental validation is needed. 

Graphical abstract
Keywords
Alzheimer’s disease
Cholinesterase inhibitors
Glutamate inhibitors
Molecular docking
In silico studies
Network biology
Drug repurposing
Funding
None.
Conflict of interest
The author declares no competing interests.
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