Investigating the impact of aspartame on Alzheimer’s disease through network toxicology and molecular docking

TL;DR

This study explores how aspartame might contribute to Alzheimer's disease by analyzing its molecular interactions and potential effects on key biological processes.

Contribution

The study introduces a novel computational approach combining network toxicology and molecular docking to investigate aspartame's potential role in Alzheimer's disease.

Findings

Seventy-five common targets were identified between aspartame and Alzheimer's disease, including BCL2, PPARG, and TNF.

Aspartame is speculated to influence Alzheimer's disease through pathways related to neuroinflammation, apoptosis, and oxidative stress.

Molecular docking suggests aspartame has binding affinity with core targets linked to Alzheimer's disease pathogenesis.

Abstract

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder, and the relationship between its pathogenesis and environmental factors has garnered increasing scholarly interest. Aspartame, a widely utilized artificial sweetener, has potential neurotoxic effects that remain incompletely understood. This study employs network toxicology and molecular docking to speculate on the potential molecular mechanisms by which aspartame is involved in the pathological process of AD.

By integrating data from multiple databases, including ChEMBL, SwissTargetPrediction, OMIM, and GeneCards, we obtained the shared targets of aspartame and AD. A protein–protein interaction (PPI) network was constructed using the STRING database and Cytoscape software to discern the core targets. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed via the DAVID database, and molecular docking validation of the core targets was conducted using AutoDock Vina.

In this study, a total of 298 targets associated with aspartame and 2,042 targets related to AD were identified. Seventy-five common targets were discovered, with BCL2, PPARG, TNF, IL1β, MAPK3, ESR1, and CASP3 were hypothesized as key core targets. GO functional analysis indicated that these targets are predominantly involved in biological processes such as protein metabolism, neuroinflammation, apoptosis, and oxidative stress. Furthermore, KEGG pathway analysis revealed significant enrichment in pathways TNF signaling, MAPK signaling, and PI3K-Akt signaling, among others. Molecular docking studies have shown that aspartame has A certain binding affinity with some core targets.

It is speculated that aspartame may be involved in the key pathological processes of AD through multi-target and multi-pathway mechanisms, including neuroinflammation, apoptosis and amyloid-beta (Aβ) metabolism. This computational study speculates that aspartame, as an environmental exposure factor, is involved in the potential molecular mechanism of AD pathogenesis, thereby providing a theoretical basis for evaluating its neurotoxicity. Further experimental studies are needed in the future to confirm its biological effects.

Figures