{
  "abstract": "The G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene is a major risk factor for the development of Parkinson’s disease (PD). LRRK2, although expressed in different cell types, is highly abundant in cells of the innate immune system. Given the importance of central and peripheral immune cells in the development of PD, we sought to investigate the consequences of the G2019S mutation on microglial and monocyte transcriptome and function. We have generated large-scale transcriptomic profiles of isogenic human induced microglial cells (iMGLs) and patient derived monocytes carrying the G2019S mutation in untreated culture conditions and following exposure to the proinflammatory factors IFNγ and LPS. We demonstrate that the G2019S mutation exerts a profound impact on the transcriptomic profile of these myeloid cells, and describe corresponding functional differences in iMGLs. The G2019S mutation led to an upregulation in lipid metabolism and phagolysosomal pathway genes in untreated and LPS/IFNγ stimulated iMGLs, which was accompanied by an increased phagocytic capacity of myelin debris. We also identified dysregulation of cell cycle genes, with a downregulation of the E2F4 regulon. Transcriptomic characterization of human-derived monocytes carrying the G2019S mutation confirmed alteration in lipid metabolism associated genes. Altogether, these findings reveal the influence of G2019S on the dysregulation of the myeloid cell transcriptome under proinflammatory conditions.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12974-026-03967-0.",
  "abstract_shown": true,
  "affiliations": [
    "Nash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY United States of America",
    "Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY United States of America",
    "Department of Genetics and Genomic Sciences & Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY United States of America",
    "Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY United States of America",
    "Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Investigacion en Neuroquimica, Universidad Complutense, Madrid, Spain",
    "Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain",
    "Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS), Madrid, Spain",
    "New York University Grossman School of Medicine, New York, NY United States of America",
    "Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL 60612 United States of America",
    "Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612 United States of America",
    "Bonnie and Tom Strauss Center for Movement Disorders, Clinical Neurosciences Center, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY United States of America"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3,
        4,
        5,
        6
      ],
      "name": "Elisa Navarro"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Anastasia G. Efthymiou"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Daniele Mattei"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Madison Parks"
    },
    {
      "affs": [
        7
      ],
      "name": "Giulietta Maria Riboldi"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        8,
        9
      ],
      "name": "Ricardo A. Vialle"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Evan Udine"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Benjamin Z. Muller"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jack Humphrey"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Amanda Allan"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Charalambos Argyrou"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        8,
        9
      ],
      "name": "Katia de Paiva Lopes"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Alexandra Münch"
    },
    {
      "affs": [
        3,
        10
      ],
      "name": "Deborah Raymond"
    },
    {
      "affs": [
        3,
        10
      ],
      "name": "Rivka Sachdev"
    },
    {
      "affs": [
        3,
        10
      ],
      "name": "Vicki L. Shanker"
    },
    {
      "affs": [
        3,
        10
      ],
      "name": "Joan Miravite"
    },
    {
      "affs": [
        3,
        10
      ],
      "name": "Viktoriya Katsnelson"
    },
    {
      "affs": [
        3,
        10
      ],
      "name": "Katherine Leaver"
    },
    {
      "affs": [
        7
      ],
      "name": "Steven Frucht"
    },
    {
      "affs": [
        3,
        10
      ],
      "name": "Susan B. Bressman"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Edoardo Marcora"
    },
    {
      "affs": [
        3,
        10
      ],
      "name": "Rachel Saunders-Pullman"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Alison M. Goate"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Towfique Raj"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bp62b0z0kzfvy.bib",
  "cited_by": 6,
  "doi": "10.1186/s12974-026-03967-0",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733072/",
  "id": "bp62b0z0kzfvy",
  "issns": [
    "1742-2094"
  ],
  "landing_url": "https://doi.org/10.1186/s12974-026-03967-0",
  "language": "en",
  "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": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W4399256360",
  "pdf_url": null,
  "pmcid": "PMC13733072",
  "pmid": "42983839",
  "published": "2026-08-08",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/bp62b0z0kzfvy.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:56Z",
      "native_id": "PMC13733072",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12974-026-03967-0"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "LRRK2 G2019S variant is associated with transcriptional changes in Parkinson’s disease human myeloid cells under proinflammatory environment",
  "title_text": "LRRK2 G2019S variant is associated with transcriptional changes in Parkinson’s disease human myeloid cells under proinflammatory environment",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:56Z",
  "url": "https://research.draconitic.com/paper/bp62b0z0kzfvy",
  "venue": "Journal of Neuroinflammation",
  "versions": []
}