{
  "abstract": "Excessive accumulation of reactive oxygen species (ROS) in the brain and the resulting oxidative stress are core drivers of neurodegenerative processes. Human dental pulp stem cells (DPSCs) secrete small extracellular vesicles (sEVs) abundant in functional microRNAs, which possess prominent regenerative capacity. The present study investigated the neuroprotective effects of DPSC-derived sEVs (DPSC-sEVs) against oxidative injury in SH-SY5Y neuronal cells and elucidated the underlying molecular mechanisms. DPSC identity was confirmed via flow cytometric immunophenotyping and multipotent differentiation assays. sEVs were isolated from DPSC-conditioned medium and characterized by transmission electron microscopy, nanoparticle tracking analysis and detection of canonical exosomal markers (CD63, CD81, and TSG101). An in vitro model of neuronal oxidative stress was established using hydrogen peroxide (H2O2). Cell viability, apoptosis, intracellular ROS levels, and lactate dehydrogenase (LDH) release, as well as the levels/activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), were assessed to evaluate the protective effects of sEVs. Candidate miRNAs in sEVs were screened by quantitative real-time PCR (qPCR). Direct binding of miR-100-5p to the 3′ untranslated region (3′UTR) of mammalian target of rapamycin (mTOR) was verified via dual-luciferase reporter assay. Autophagic activity was evaluated by immunoblotting and immunofluorescence staining of LC3B/p62. Pretreatment with DPSC-sEVs significantly ameliorated H2O2-induced neuronal oxidative damage and apoptosis. Mechanistically, sEV miR-100-5p conferred neuroprotective and antioxidant properties by inhibiting mTOR signaling and activating autophagy in vitro. Blockade of miR-100-5p or pharmacological inhibition of autophagy by 3-methyladenine (3-MA) largely abolished these protective effects. In conclusion, DPSC-sEVs attenuate neuronal oxidative stress by reversing mTOR-mediated suppression of autophagy, and this protective effect is dependent on the function of miR-100-5p in SH-SY5Y cells. The miR-100-5p/mTOR/autophagy axis mediates the neuroprotective effects of DPSC-sEVs, representing a promising therapeutic candidate for oxidative stress-associated neurodegenerative diseases that merits further in vivo validation.",
  "abstract_shown": true,
  "affiliations": [
    "School of Life Sciences and Medicine, Shandong University of Technology, 266 Xincun West Road, Zhangdian, Zibo 255049, China",
    "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute, Gannan Medical University, Ganzhou 341000, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wenli Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanfang Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Fengtang Yang",
      "orcid": "0000-0002-3573-2354"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wensheng Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiuzhen Zhang",
      "orcid": "0000-0002-6555-072X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f540qng247ceh.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15201843",
  "fulltext_url": "https://europepmc.org/articles/PMC13702593",
  "id": "f540qng247ceh",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/20/1843",
  "language": "eng",
  "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",
      "1312|Extracellular vesicles in disease"
    ]
  ],
  "openalex": "W7221514758",
  "pdf_url": "https://europepmc.org/articles/PMC13702593?pdf=render",
  "pmcid": "PMC13702593",
  "pmid": "42929816",
  "published": "2026-10-11",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/f540qng247ceh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15201843",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/20/1843"
    },
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42929816",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42929816"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Extracellular vesicles in disease",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Dental Pulp Stem Cell-Derived Small Extracellular Vesicle miR-100-5p Attenuates Neuronal Oxidative Stress via Regulating the mTOR-Autophagy Signaling Axis",
  "title_text": "Dental Pulp Stem Cell-Derived Small Extracellular Vesicle miR-100-5p Attenuates Neuronal Oxidative Stress via Regulating the mTOR-Autophagy Signaling Axis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/f540qng247ceh",
  "venue": "Cells",
  "versions": []
}