{
  "abstract": "Endothelial cell dysfunction is a major driver of neuroinflammation, a critical contributor to neurological disorders. Non-muscle myosin IIA (NMIIA), a key cytoskeletal protein, has been implicated in cerebrovascular pathology, but its role in endothelial-mediated neuroinflammation remains unclear. This study reveals that NMIIA expression is downregulated in brain microvascular endothelial cells during aging. Using in vitro knockdown and endothelial-specific conditional knockout mouse models, we demonstrate that NMIIA deficiency specifically upregulates VCAM-1 protein without affecting its mRNA or other inflammatory mediators. Mechanistically, NMIIA loss impairs autophagic flux, particularly the autophagosome-lysosome fusion, leading to inhibited autophagic degradation and subsequent accumulation of VCAM-1. Proteomic analysis and biochemical assays identified Caveolin-1 (Cav-1) as a direct binding partner of NMIIA. NMIIA deficiency promotes the redistribution of the autophagy-related protein ATG5 into Cav-1-enriched lipid raft domains, a process known to suppress autophagy initiation. Functionally, soluble VCAM-1 released from NMIIA-deficient endothelial cells promotes pro-inflammatory polarization of microglia and induces neuronal apoptosis in vitro. In vivo, NMIIA iECKO mice exhibit increased microglial activation, impaired hippocampal neurogenesis, neuronal loss, and significant deficits in learning and memory behaviors. Collectively, our findings define a novel NMIIA–Cav-1–autophagy–VCAM-1 regulatory axis in brain endothelium, positioning NMIIA as a crucial maintainer of neurovascular homeostasis by preventing VCAM-1-driven neuroinflammation. This pathway provides new mechanistic insights into aging-related cerebrovascular dysfunction and offers potential therapeutic targets for neuroinflammatory diseases.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Haiyi Zhang"
    },
    {
      "name": "Yawei Li"
    },
    {
      "name": "Xinhong Zhao"
    },
    {
      "name": "Yujie Zhao"
    },
    {
      "name": "Jinchao Gu"
    },
    {
      "name": "Hao Pan"
    },
    {
      "name": "Aijun Liu"
    },
    {
      "name": "Jiangguo Lin"
    },
    {
      "name": "Yuanyuan Peng"
    },
    {
      "name": "Lijun Wang"
    },
    {
      "name": "Huantian Zhang"
    },
    {
      "name": "Jiahui Cao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/03mf1b93kjybp.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-75768-7",
  "fulltext_url": null,
  "id": "03mf1b93kjybp",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://www.nature.com/articles/s41598-026-75768-7",
  "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",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7223348336",
  "pdf_url": "https://www.nature.com/articles/s41598-026-75768-7_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-24",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/03mf1b93kjybp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:33Z",
      "native_id": "10.1038/s41598-026-75768-7",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41598-026-75768-7"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Neuroinflammation and Neurodegeneration Mechanisms",
      "subfield": "neurology"
    }
  ],
  "title": "Deficiency of non-muscle myosin IIA promotes neuroinflammation by impairing autophagic degradation of VCAM-1 in brain endothelium",
  "title_text": "Deficiency of non-muscle myosin IIA promotes neuroinflammation by impairing autophagic degradation of VCAM-1 in brain endothelium",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:33Z",
  "url": "https://research.draconitic.com/paper/03mf1b93kjybp",
  "venue": "Scientific Reports",
  "versions": []
}