{
  "abstract": "Aspartame, a widely used artificial sweetener, has raised significant concerns regarding its safety, especially in light of the rising incidence of Alzheimer’s Disease (AD). However, systematic investigations into aspartame’s potential neurotoxicity and its role in AD pathology remain limited. In this study, we employed an integrated approach combining network toxicology predictions, molecular docking, and in vitro validation to explore the neurotoxic mechanisms of aspartame in AD. By analyzing multiple public databases through network toxicology, we identified 185 common targets between aspartame and AD. Protein-protein interaction (PPI) network analysis further highlighted 10 core hub genes, including KDR, CCNE1, and GSK-3β. Molecular docking predicted favorable interactions for key targets such as GSK-3β (−5.002 kcal/mol) and KDR (−5.613 kcal/mol), with other hubs showing moderate binding affinities. In vitro experiments demonstrated that aspartame dose-dependently reduced BV2 microglial cell viability and triggered a pro-inflammatory response. Specifically, aspartame increased the production of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), while upregulating the expression of GSK-3β, iNOS, TNF-α, IL-1β, and IL-6, similar to LPS-induced inflammation. These findings suggest that aspartame may induce a pro-inflammatory response in BV2 microglial cells through multiple signaling pathways, although the relevance of these findings to human neurological safety remains to be established. This study provides a basis for further investigation into the neurological safety of aspartame and proposes a novel paradigm for evaluating the neurotoxic potential of food additives using an integrated systems toxicology approach.",
  "abstract_shown": true,
  "affiliations": [
    "School of Nursing, Guangxi Medical University, Nanning, China",
    "Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China",
    "Guangxi Key Laboratory of Artificial Intelligence for Genetic Diseases of Long-dwelling Nationalities, Youjiang Medical University for Nationalities, Baise, China",
    "Institute of Life Sciences, Guangxi Medical University, Nanning, China",
    "Department of Orthopedic, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dongyang Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Xuejun Weng"
    },
    {
      "affs": [
        0
      ],
      "name": "Yijuan Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Dongni Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "Shunhan Yao"
    },
    {
      "affs": [
        3
      ],
      "name": "Weihao Zheng"
    },
    {
      "affs": [
        4
      ],
      "name": "Xiaohong Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yilin Wei"
    },
    {
      "affs": [
        3
      ],
      "name": "Sheng Xu",
      "orcid": "0009-0009-9044-2147"
    },
    {
      "affs": [
        1
      ],
      "name": "Chunwei Wei"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/76vgzjam5m0gv.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0361766",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13730326/",
  "id": "76vgzjam5m0gv",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0361766",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Alzheimer's Disease"
    ],
    [
      "heading",
      "Animal Cells"
    ],
    [
      "heading",
      "Biochemistry"
    ],
    [
      "heading",
      "Biology and Life Sciences"
    ],
    [
      "heading",
      "Cell Biology"
    ],
    [
      "heading",
      "Cellular Types"
    ],
    [
      "heading",
      "Chemistry"
    ],
    [
      "heading",
      "Clinical Medicine"
    ],
    [
      "heading",
      "Computational Chemistry"
    ],
    [
      "heading",
      "Computer and Information Sciences"
    ],
    [
      "heading",
      "Dementia"
    ],
    [
      "heading",
      "Gene Expression"
    ],
    [
      "heading",
      "Genetics"
    ],
    [
      "heading",
      "Glial Cells"
    ],
    [
      "heading",
      "Immune Response"
    ],
    [
      "heading",
      "Immunology"
    ],
    [
      "heading",
      "Inflammation"
    ],
    [
      "heading",
      "Medical Conditions"
    ],
    [
      "heading",
      "Medicine and Health Sciences"
    ],
    [
      "heading",
      "Mental Health and Psychiatry"
    ],
    [
      "heading",
      "Microglial Cells"
    ],
    [
      "heading",
      "Molecular Docking"
    ],
    [
      "heading",
      "Network Analysis"
    ],
    [
      "heading",
      "Neurochemicals"
    ],
    [
      "heading",
      "Neurochemistry"
    ],
    [
      "heading",
      "Neurodegenerative Diseases"
    ],
    [
      "heading",
      "Neurology"
    ],
    [
      "heading",
      "Neuroscience"
    ],
    [
      "heading",
      "Nitric Oxide"
    ],
    [
      "heading",
      "Pathology and Laboratory Medicine"
    ],
    [
      "heading",
      "Physical Sciences"
    ],
    [
      "heading",
      "Protein Interaction Networks"
    ],
    [
      "heading",
      "Proteomics"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "Signs and Symptoms"
    ],
    [
      "heading",
      "Toxicology"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Neurochemistry/Neurochemicals/Nitric oxide"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteomics/Protein interaction networks"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Glial cells/Microglial cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune response/Inflammation"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Neurochemistry/Neurochemicals/Nitric oxide"
    ],
    [
      "plos",
      "/Biology and life sciences/Toxicology"
    ],
    [
      "plos",
      "/Computer and information sciences/Network analysis/Protein interaction networks"
    ],
    [
      "plos",
      "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Inflammation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response/Inflammation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Neurodegenerative diseases/Alzheimer's disease"
    ],
    [
      "plos",
      "/Medicine and health sciences/Mental health and psychiatry/Dementia/Alzheimer's disease"
    ],
    [
      "plos",
      "/Medicine and health sciences/Neurology/Dementia/Alzheimer's disease"
    ],
    [
      "plos",
      "/Medicine and health sciences/Neurology/Neurodegenerative diseases/Alzheimer's disease"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Toxicology"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Computational chemistry/Molecular docking"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": "PMC13730326",
  "pmid": "42976132",
  "published": "2026-11-03",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/76vgzjam5m0gv.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:43Z",
      "native_id": "10.1371/journal.pone.0361766",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0361766"
    },
    {
      "first_seen": "2026-11-07T12:22:54Z",
      "native_id": "PMC13730326",
      "source": "pmc",
      "url": "https://doi.org/10.1371/journal.pone.0361766"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Cell Biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    },
    {
      "field": "chemistry",
      "origin": "heading:Computational Chemistry",
      "subfield": "theoretical"
    },
    {
      "field": "medicine",
      "origin": "plos:neurology",
      "subfield": "neurology"
    },
    {
      "field": "medicine",
      "origin": "plos:toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Unveiling the neuroinflammatory potential of aspartame in Alzheimer’s disease: A comprehensive network toxicology and experimental validation approach",
  "title_text": "Unveiling the neuroinflammatory potential of aspartame in Alzheimer’s disease: A comprehensive network toxicology and experimental validation approach",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:22:54Z",
  "url": "https://research.draconitic.com/paper/76vgzjam5m0gv",
  "venue": "PLOS One",
  "versions": []
}