{
  "abstract": "Parkinson's disease (PD) is a global health problem that urgently requires deeper mechanistic insights. Mutations in the ATPase cation transporting 13A2 (ATP13A2) gene are linked to autosomal recessive PD, yet the pathological roles of this gene remain incompletely defined. Previous studies on ATP13A2 have focused mainly on its lysosomal functions in neurons, whereas its role in astrocytes has been largely overlooked. Here, we investigated how ATP13A2 affects astrocytic mitochondrial function and contributes to PD pathology. Using PD mice and Atp13a2 knockout mice, we found that loss of Atp13a2 disrupts mitochondrial morphology and dynamics in the substantia nigra, with astrocytes showing both excessive fission and activation. We further found that Atp13a2 deficiency caused excessive mitochondrial fission, elevated reactive oxygen species (ROS) levels, and promoted extracellular double-stranded DNA release. ELISA measurements revealed significantly increased secretion of IL-1β, IL-6, and TNF-α, indicating increased release of pro-inflammatory cytokines. Importantly, both pharmacological inhibition of fission via Mdivi-1 and Atp13a2 overexpression restored mitochondrial dynamics homeostasis, suppressed oxidative stress, and reduced cytokine secretion. Collectively, these findings demonstrate that ATP13A2 preserves the mitochondrial fission-fusion balance in astrocytes; its loss breaks this balance, thereby triggering neuroinflammation. By uncovering previously unrecognized roles of ATP13A2 in regulating mitochondrial fission and subsequent neuroinflammation, this study provides new insights into PD pathogenesis and identifies potential molecular targets for therapy. These findings open fresh avenues for developing more effective strategies to modify PD progression.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, China.",
    "College of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu, China.",
    "Department of Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.",
    "The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Chen Qiao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Huajun Mo"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiangqi Hu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tao Dang"
    },
    {
      "affs": [
        0
      ],
      "name": "Fenglan Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Dan Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "Jiang Ni"
    },
    {
      "affs": [
        3
      ],
      "name": "Linxiao Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3khk076dpcttz.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1959910",
  "fulltext_url": "https://europepmc.org/articles/PMC13713819",
  "id": "3khk076dpcttz",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42952843",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7221749669",
  "pdf_url": "https://europepmc.org/articles/PMC13713819?pdf=render",
  "pmcid": "PMC13713819",
  "pmid": "42952843",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/3khk076dpcttz.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42952843",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42952843"
    },
    {
      "first_seen": "2026-11-01T12:21:25Z",
      "native_id": "PMC13713819",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1959910"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Astrocytic ATP13A2 modulates neuroinflammatory responses via mitochondrial fission in Parkinson's disease.",
  "title_text": "Astrocytic ATP13A2 modulates neuroinflammatory responses via mitochondrial fission in Parkinson's disease.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:25Z",
  "url": "https://research.draconitic.com/paper/3khk076dpcttz",
  "venue": "Frontiers in cell and developmental biology",
  "versions": []
}