{
  "abstract": "Astrocytes participate in the clearance of obsolete or unwanted neuronal synapses. However, the molecular machinery involved in synapse recognition remains unclear, particularly in pathological conditions. Here, we investigated the phagocytic process of astrocytes through individual gene silencing using a druggable gene library. Our study demonstrates that the Atypical chemokine receptor 3 (Ackr3) is a major player of astrocyte-mediated synapse engulfment. Mechanistically, we showed that Ackr3 recognizes phosphatidylethanolamine (PE)-bound C-X-C motif chemokine 12 (CXCL12) at synaptic terminals, thus serving as a novel marker of synaptic dysfunction. Notably, both ACKR3 and CXCL12 are upregulated in post-mortem brains of Alzheimer's disease (AD) patients, and AD mouse models. Genetic downregulation of Ackr3 in AD mice significantly reduces astrocyte-mediated synaptic elimination and rescues pathological phenotypes, including synapse loss and cognitive impairment. Overall, this work unveils a novel, possibly targetable mechanism of astrocyte-mediated synaptic engulfment implicated in neurodegenerative disease.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biology, University of Padova, Padova, Italy",
    "Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Republic of Korea",
    "Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea",
    "IRCCS San Camillo Hospital, Venice, Italy",
    "Achucarro Basque Centre for Neuroscience, The Basque Biomodels Platform for Human Research Leioa, Spain",
    "National Research Council (CNR), Institute of Neuroscience, Pisa, Italy",
    "Stella Maris Foundation, IRCCS, Calambrone, Pisa, Italy",
    "Department of Neuroscience, University of Padova, Padova 35121, Italy",
    "Section of Human Anatomy, Department of Neurosciences, University of Padova, Padua, Italy",
    "Study Center for Neurodegeneration (CESNE), Padova, Italy",
    "VIB-KU Leuven Center for Brain & Disease Research, Campus Gasthuisberg, Leuven, Belgium",
    "Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland",
    "Fundación Biofisica Bizkaia, Leioa, Spain"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Veronica Giusti",
      "orcid": "0000-0002-1467-4407"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Jungjoo Park",
      "orcid": "0000-0002-0548-9736"
    },
    {
      "affs": [
        3
      ],
      "name": "Elena Giusto",
      "orcid": "0000-0003-0562-1466"
    },
    {
      "affs": [
        0
      ],
      "name": "Laura Masatti",
      "orcid": "0009-0002-2610-4265"
    },
    {
      "affs": [
        4
      ],
      "name": "Paula Ramos‐Gonzalez",
      "orcid": "0000-0003-4825-5769"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Ludovica Iovino",
      "orcid": "0000-0001-6373-3541"
    },
    {
      "affs": [
        7
      ],
      "name": "Michele Sandre",
      "orcid": "0000-0002-3013-6908"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Aron Emmi",
      "orcid": "0000-0002-2796-5676"
    },
    {
      "affs": [
        0
      ],
      "name": "Gurkirat Kaur",
      "orcid": "0009-0002-1377-1608"
    },
    {
      "affs": [
        3
      ],
      "name": "Erika Coletto",
      "orcid": "0000-0002-6709-4668"
    },
    {
      "affs": [
        10
      ],
      "name": "Z. Van Acker"
    },
    {
      "affs": [
        10
      ],
      "name": "Wim G. Annaert",
      "orcid": "0000-0003-0150-9661"
    },
    {
      "affs": [
        0
      ],
      "name": "Enrica Calura",
      "orcid": "0000-0001-8463-2432"
    },
    {
      "affs": [
        11
      ],
      "name": "Francesco Petrelli",
      "orcid": "0000-0003-0696-7039"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Andrea Porzionato",
      "orcid": "0000-0003-3025-4717"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Raffaele De",
      "orcid": "0000-0002-2307-0277"
    },
    {
      "affs": [
        4,
        12
      ],
      "name": "Fabio Cavaliere",
      "orcid": "0000-0003-2003-522X"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "WS Chung"
    },
    {
      "affs": [
        0,
        3,
        9
      ],
      "name": "Laura Civiero",
      "orcid": "0000-0002-5334-155X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2bqaxh7rqcv0g.bib",
  "cited_by": 6,
  "doi": "10.1186/s13024-026-00976-8",
  "fulltext_url": null,
  "id": "2bqaxh7rqcv0g",
  "issns": [
    "1750-1326"
  ],
  "landing_url": "https://doi.org/10.1186/s13024-026-00976-8",
  "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",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W4400380659",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "42458598",
  "published": "2026-07-15",
  "publisher": "BioMed Central",
  "ris": "https://research.draconitic.com/paper/2bqaxh7rqcv0g.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T13:20:36Z",
      "native_id": "W4400380659",
      "source": "openalex",
      "url": "https://doi.org/10.1186/s13024-026-00976-8"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Neuroinflammation and Neurodegeneration Mechanisms",
      "subfield": "neurology"
    }
  ],
  "title": "Atypical chemokine receptor 3 regulates synaptic removal in disease astrocytes",
  "title_text": "Atypical chemokine receptor 3 regulates synaptic removal in disease astrocytes",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:14Z",
  "url": "https://research.draconitic.com/paper/2bqaxh7rqcv0g",
  "venue": "Molecular Neurodegeneration",
  "versions": []
}