{
  "abstract": "The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a central mediator of cytosolic DNA-induced innate immune responses, driving the production of type I IFNs and pro-inflammatory cytokines. Beyond its canonical role in cytosolic DNA sensing, increasing attention has been directed toward the noncanonical functions of cGAS and STING, particularly within the nucleus. Recent studies implicate dysregulated cGAS-STING signaling in neurodegenerative diseases and brain aging, with a prominent contribution to glial activation-associated neuroinflammation, a hallmark of many neurological disorders. In this Review, we first summarize the molecular mechanisms underlying the canonical cGAS-STING pathway in DNA sensing and innate immune activation. We then discuss emerging noncanonical roles of cGAS in chromatin organization and RNA metabolism, drawing on insights from evolutionary conservation and protein interactome analyses. Finally, we outline the involvement of cGAS-STING signaling in diverse aspects of brain function, including glial state regulation, neuronal homeostasis, blood-brain barrier integrity, and peripheral immune surveillance, highlighting their contributions to neuroinflammation and neuropathology. We also summarize current pharmacological inhibitors targeting cGAS and STING and discuss their therapeutic potential for modulating cGAS-STING signaling to manage brain disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, and",
    "Physiology, Biophysics and Systems Biology graduate program, Graduate School of Medical Sciences, Weill Cornell Medicine, New York, New York, USA"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Weixi Feng"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Abulimiti Aikedan",
      "orcid": "0009-0004-5189-4013"
    },
    {
      "affs": [
        0
      ],
      "name": "Subhash C. Sinha",
      "orcid": "0000-0001-8916-5677"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Gan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bsgb9t87c82ye.bib",
  "cited_by": 6,
  "doi": "10.1172/jci204550",
  "fulltext_url": null,
  "id": "bsgb9t87c82ye",
  "issns": [
    "0021-9738",
    "1558-8238"
  ],
  "landing_url": "https://doi.org/10.1172/jci204550",
  "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",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7162933940",
  "pdf_url": "http://www.jci.org/articles/view/204550/files/pdf",
  "pmcid": "PMC13221232",
  "pmid": "42222892",
  "published": "2026-06-01",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/bsgb9t87c82ye.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:51Z",
      "native_id": "W7162933940",
      "source": "openalex",
      "url": "https://doi.org/10.1172/jci204550"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|interferon and immune responses",
      "subfield": "immunology"
    }
  ],
  "title": "Expanding roles of cGAS-STING signaling in neuroinflammation",
  "title_text": "Expanding roles of cGAS-STING signaling in neuroinflammation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:46Z",
  "url": "https://research.draconitic.com/paper/bsgb9t87c82ye",
  "venue": "Journal of Clinical Investigation",
  "versions": []
}