{
  "abstract": "Alzheimer’s disease (AD) is a complex neurodegenerative disorder with multifaceted pathogenesis. Given the clinical need for multi-target interventions, this study elucidated the neuroprotective mechanisms of walnut (Juglans regia L.) against AD-related cognitive impairment. Methods: We characterized 25 bioactive constituents (fatty acids and ellagitannins) and constructed a protein–protein interaction (PPI) network. GO/KEGG enrichment, integrated with Ingenuity Pathway Analysis (IPA), deciphered pharmacological pathways, followed by molecular docking to evaluate ligand–target binding thermodynamics. Network analysis revealed that walnut phytochemicals synergistically modulate the MAPK-mTORC1-TFEB-mediated endolysosomal homeostasis pathway. Molecular docking indicated that ellagitannins (strictinin, pedunculagin, tellimagrandin I) exhibit robust affinities for upstream RAS/RAF/MEK kinases, suppressing pro-pathogenic signaling. Concurrently, gallic acid targeted ABCA1 and TFEB, promoting TFEB activation and nuclear translocation to enhance beta-amyloid clearance and lysosomal biogenesis. This study provides evidence that walnut attenuates AD pathology through “multi-component” reinforcement of the endolysosomal defense system, establishing a mechanistic foundation for walnut as a promising functional food.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chinese Medicine, E-Da Cancer Hospital, Kaohsiung 82445, Taiwan",
    "Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan",
    "School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 84001, Taiwan",
    "Department of Chinese Medicine, Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan",
    "Linsen Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei 10450, Taiwan"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Chih-Ting Lin",
      "orcid": "0000-0001-5117-2791"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Kuan-Tso Chen"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Yu-Chiang Hung",
      "orcid": "0000-0001-7490-4465"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/erf4aj5tmmhbs.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27188288",
  "fulltext_url": null,
  "id": "erf4aj5tmmhbs",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/18/8288",
  "language": null,
  "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": [
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7214424411",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/erf4aj5tmmhbs.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27188288",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/18/8288"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Exploring the Neuroprotective Effects of Walnut (Juglans regia L.) Against Cognitive Impairment in Alzheimer’s Disease Through the MAPK-mTORC1-TFEB-Mediated Endolysosomal Pathway: A Network Pharmacology and Molecular Docking Approach",
  "title_text": "Exploring the Neuroprotective Effects of Walnut (Juglans regia L.) Against Cognitive Impairment in Alzheimer’s Disease Through the MAPK-mTORC1-TFEB-Mediated Endolysosomal Pathway: A Network Pharmacology and Molecular Docking Approach",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:55Z",
  "url": "https://research.draconitic.com/paper/erf4aj5tmmhbs",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}