{
  "abstract": "Tunneling nanotubes (TNTs) enable direct intercellular transfer of macromolecules, organelles, and pathogenic protein aggregates. While α-synuclein (α-Syn) aggregates are known to promote TNT formation, the underlying mechanisms remain poorly defined. Here, using human neuronal and microglial cell lines, as well as iPSC-derived dopaminergic neurons and microglia, we show that α-Syn aggregates induce severe mitochondrial damage, leading to cytosolic release of mitochondrial DNA (mtDNA) and activation of the cGAS-STING-NF-κB-IRF3 pathway. This innate immune response drives actin cytoskeleton remodeling and the formation of TNT-like structures, promoting intercellular transfer of α-Syn from neurons to microglia. Additionally, neuronal cells transfer damaged mitochondria to microglia, where they undergo lysosome-mediated degradation. Neuron-to-microglia communication under α-Syn-induced stress also triggers a bystander inflammatory response in microglia, suggesting a neuroimmune activation. Our findings identify mitochondrial damage and STING-mediated inflammation as key drivers of TNT formation and α-Syn propagation, highlighting potential targets to modulate disease progression in Synucleinopathies.",
  "abstract_shown": true,
  "affiliations": [
    "Institut Pasteur, Université Paris Cité, CNRS UMR 3691, Membrane Traffic and Pathogenesis, Paris, France",
    "Université Paris-Saclay, Gif-sur-Yvette, France",
    "Institut Pasteur, Université Paris Cité, CNRS UMR 369, Membrane Traffic and Pathogenesis, F-7505 Paris, France",
    "Université Paris-Saclay, 91190 Gif-sur-Yvette, France",
    "Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital-IDIBELL, Barcelona, Spain",
    "Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain",
    "Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital- IDIBELL, 08908 Hospitalet de Llobregat, Spain",
    "Institute of Biomedicine of the University of Barcelona (IBUB), Carrer Baldiri Reixac 15-21, Barcelona 08028, Spain",
    "Dementia Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan",
    "Institut Pasteur, Université Paris Cité, CNRS UMR 3691, Membrane Traffic and Pathogenesis, Paris, France. chiara.zurzolo@pasteur.fr",
    "Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Ranabir Chakraborty",
      "orcid": "0000-0002-0029-3996"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Stephanie Maya",
      "orcid": "0000-0001-7321-9706"
    },
    {
      "affs": [
        4,
        5,
        6,
        7
      ],
      "name": "Veronica Testa",
      "orcid": "0000-0001-9041-7325"
    },
    {
      "affs": [
        4,
        5,
        6,
        7
      ],
      "name": "Jara Montero-Muñoz",
      "orcid": "0000-0002-6877-4833"
    },
    {
      "affs": [
        8
      ],
      "name": "Takashi Nonaka",
      "orcid": "0000-0002-0830-9403"
    },
    {
      "affs": [
        8
      ],
      "name": "Masato Hasegawa",
      "orcid": "0000-0001-7415-8159"
    },
    {
      "affs": [
        4,
        5,
        6,
        7
      ],
      "name": "Antonella Consiglio",
      "orcid": "0000-0002-3988-6254"
    },
    {
      "affs": [
        9,
        10,
        2
      ],
      "name": "Chiara Zurzolo",
      "orcid": "0000-0001-6048-6602"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1z3zz437hg9zz.bib",
  "cited_by": 10,
  "doi": "10.1038/s41467-026-73136-7",
  "fulltext_url": null,
  "id": "1z3zz437hg9zz",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-73136-7",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W4411590030",
  "pdf_url": null,
  "pmcid": "PMC13376753",
  "pmid": "42140967",
  "published": "2026-05-15",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/1z3zz437hg9zz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:56Z",
      "native_id": "W4411590030",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-73136-7"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "α-Synuclein aggregates induce mitochondrial damage and trigger innate immunity to drive neuron–microglia communication",
  "title_text": "α-Synuclein aggregates induce mitochondrial damage and trigger innate immunity to drive neuron–microglia communication",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:16Z",
  "url": "https://research.draconitic.com/paper/1z3zz437hg9zz",
  "venue": "Nature Communications",
  "versions": []
}