The DOI matches its Crossref record; 212 of the 212 references it cites were found in a registry or an index.
The cGAS–STING pathway as a therapeutic target in inflammatory diseases
Open accessAbstract
The cGAS-STING signalling pathway has emerged as a key mediator of inflammation in the settings of infection, cellular stress and tissue damage. Underlying this broad involvement of the cGAS-STING pathway is its capacity to sense and regulate the cellular response towards microbial and host-derived DNAs, which serve as ubiquitous danger-associated molecules. Insights into the structural and molecular biology of the cGAS-STING pathway have enabled the development of selective small-molecule inhibitors with the potential to target the cGAS-STING axis in a number of inflammatory diseases in humans. Here, we outline the principal elements of the cGAS-STING signalling cascade and discuss the general mechanisms underlying the association of cGAS-STING activity with various autoinflammatory, autoimmune and degenerative diseases. Finally, we outline the chemical nature of recently developed cGAS and STING antagonists and summarize their potential clinical applications.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These include retrotransposable elements (for example, LINE-1), cytosolic mitochondrial DNA, or circular DNA—all of which can activate the cytosolic DNA-sensing (cGAS)-STING pathway, triggering the expression of pro-inflammatory genes79–81.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [81]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In 2008, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) DNA-sensing pathway has been discovered as a vital mediator in detecting the misplaced or foreign DNA and triggering the release of type I interferons and other immune mediators.388,389”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [388]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“cGAS can sense cytosolic DNA,390 allosterically activate its catalytic activity and induce the synthesis of second messenger molecule, 2′3′ cyclic GMP–AMP (cGAMP).388”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [388]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The SASP of senescent cells is not static; it can change over time78–80 and varies depending on the type of cells that became senescent and how senescence was induced16,44,59,60,81.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [81]
Experimental — accuracy not yet measuredIn the citing paper
“Senescence-associated DNA damage is sensed via the cGAS–STING pathway, which activates the transcription factors interferon regulatory factor 3 (IRF3) and NF-κB, thereby inducing an interferon and SASP response55–58”
From COVID-19 and cellular senescence (2023) · cites this paper as [58]
In the citing paper
“inhibiting cGAS/STING signaling downstream of CCF activation may be beneficial in the context of chronic inflammation with age (Decout et al., 2021)”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Decout et al., 2021
In the citing paper
“NF‐κB regulates cell proliferation, apoptosis and survival of normal cells, thus acting as a crucial stimulator of the inflammatory response.”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [255]
In the citing paper
“Additionally, NF‐κB promotes the development of inflammation, tumors and immune dysfunction [255].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [255]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
3 retracted
RETRACTED ARTICLE: Parkin and PINK1 mitigate STING-induced inflammation
Sliter, D. A., Martinez, J., Hao, L., Chen, X., Sun, N., Fischer, T. D., Burman, J. L., Li, Y., Zhang, Z., Narendra, D. P., et al. (2018) · Nature · doi:10.1038/s41586-018-0448-9 · Cited by 1,287
RetractedMartinez, J., Almendinger, J., Oberst, A., Ness, R., Dillon, C. P., Fitzgerald, P., Hengartner, M. O., & Green, D. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113421108 · Cited by 655
RetractedMartinez, J., Cunha, L. D., Park, S., Yang, M., Lu, Q., Orchard, R., Li, Q.-Z., Yan, M., Janke, L., Guy, C., et al. (2016) · Nature · doi:10.1038/nature17950 · Cited by 381
RetractedCyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
Sun, L., Wu, J., Du, F., Chen, X., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1232458 · Cited by 4,996
Mechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580
STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
Ishikawa, H., & Barber, G. N. (2008) · Nature · doi:10.1038/nature07317 · Cited by 3,576
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Ishikawa, H., Ma, Z., & Barber, G. N. (2009) · Nature · doi:10.1038/nature08476 · Cited by 2,759
Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA
Wu, J., Sun, L., Chen, X., Du, F., Shi, H., Chen, C., & Chen, Z. J. (2012) · Science · doi:10.1126/science.1229963 · Cited by 2,628
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623
Cited by
Sorted by citations
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668
“cGAS can sense cytosolic DNA,(390) allosterically activate its catalytic activity and induce the synthesis of second messenger molecule, 2′3′ cyclic GMP–AMP (cGAMP).(388) cGAMP produced by cGAS activation binds to STING which is located on the membrane of endoplasmic reticulum (ER)(391) and leads to the translocation…”
BackgroundMicrobiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
Cellular senescence and senolytics: the path to the clinic
Chaib, S., Tchkonia, T., & Kirkland, J. L. (2022) · Nature Medicine · doi:10.1038/s41591-022-01923-y · Cited by 1,134
Chronic inflammation and the hallmarks of aging
Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101755 · Cited by 471
Tumor microenvironment signaling and therapeutics in cancer progression
Goenka, A., Khan, F., Verma, B., Sinha, P., Dmello, C. C., Jogalekar, M. P., Gangadaran, P., & Ahn, B. (2023) · Cancer Communications · doi:10.1002/cac2.12416 · Cited by 323
Activation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5×FAD mice
Xie, X., Ma, G., Li, X., Zhao, J., Zhao, Z., & Zeng, J. (2023) · Nature Aging · doi:10.1038/s43587-022-00337-2 · Cited by 292
Cytoplasmic DNA: sources, sensing, and role in aging and disease
Miller, K. N., Victorelli, S. G., Salmonowicz, H., Dasgupta, N., Liu, T., Passos, J. F., & Adams, P. D. (2021) · Cell · doi:10.1016/j.cell.2021.09.034 · Cited by 288
STING mediates neurodegeneration and neuroinflammation in nigrostriatal α-synucleinopathy
Hinkle, J. T., Patel, J., Panicker, N., Karuppagounder, S. S., Biswas, D., Belingon, B., Chen, R., Brahmachari, S., Pletnikova, O., Troncoso, J. C., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2118819119 · Cited by 240
Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders
Huang, Y., Liu, B., Sinha, S. C., Amin, S., & Gan, L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00672-x · Cited by 164
COVID-19 and cellular senescence
Schmitt, C. A., Tchkonia, T., Niedernhofer, L. J., Robbins, P. D., Kirkland, J. L., & Lee, S. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00785-2 · Cited by 153
Mitophagy and cGAS–STING crosstalk in neuroinflammation
Zhou, X., Wang, J., Yu, L., Qiao, G., Qin, D., Yuen-Kwan Law, B., Ren, F., Wu, J., & Wu, A. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.05.012 · Cited by 131
Chung, S., Jeong, J.-H., Park, J.-C., Han, J. W., Lee, Y., Kim, J.-I., & Mook-Jung, I. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01295-y · Cited by 103
“At least four cGAMP import routes have been identi fi ed thus far 58 .”
Szego, E. M., Malz, L., Bernhardt, N., Rösen-Wolff, A., Falkenburger, B. H., & Luksch, H. (2022) · eLife · doi:10.7554/elife.81943 · Cited by 94
Immunopathogenic mechanisms and immunoregulatory therapies in MASLD
He, Y., Chen, Y., Qian, S., van Der Merwe, S., Dhar, D., Brenner, D. A., & Tacke, F. (2025) · Cellular & Molecular Immunology · doi:10.1038/s41423-025-01307-5 · Cited by 81
“The cyclic GMP ‒ AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, a key mediator of in fl ammation, has emerged as a critical mechanism for sensing and regulating the cellular response toward microbial and host-derived DNAs [129].”
Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway
Chen, Y., Yang, C., Miao, Y., Shi, D., Li, X., Tian, S., Zhang, Y., Xu, C., Dong, Y., Han, C., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55170-5 · Cited by 51
McFarland, K. N., & Chakrabarty, P. (2022) · Neurotherapeutics · doi:10.1007/s13311-021-01179-3 · Cited by 48
Alpha-synuclein–mediated DNA damage, STING activation, and neuroinflammation in Parkinson’s disease
Standaert, D. G., & Childers, G. M. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2204058119 · Cited by 40
Cui, Y., Liu, J., Song, Y., Chen, C., Shen, Y., & Xie, K. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70305 · Cited by 18
Alshebremi, M., Tomchuck, S. L., Myers, J. T., Kingsley, D. T., Eid, S., Abiff, M., Bonner, M., Saab, S. T., Choi, S. H., & Huang, A. Y.-C. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-006608 · Cited by 14
“32 38–40 The cytosolic dsDNA activates cGAS in tumor cells, leading to cGAMP production 41 42 which is exported as a paracrine immu-notransmitter, subjected to degradation by extracellular hydrolase, ENPP1, 43 and imported into host myeloid cells through the SLC19A1 transporter, 41 44 thereby…”
Metadata
- Authors
- Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Ifm Therapeutics (United States) (US)
- Corresponding author
- Ablasser, Andrea
- Venue
- Nature Reviews Immunology
- Published
- 2021-04-08
- Volume
- 21
- Issue
- 9
- Pages
- 548-569
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC8029610
- OpenAlex
- W3145334405
- Cited by
- 2,309
- References
- 212
- Citations by year
- 2026: 514 · 2025: 598 · 2024: 566 · 2023: 382 · 2022: 204 · 2021: 43
- FWCI
- 30.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (159836, 31003A)
- H2020 European Research Council (804933)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- cGAS-STING pathway, cytosolic DNA sensing, innate immunity, inflammatory diseases, autoimmune disease, autoinflammatory disease, degenerative diseases, small molecule inhibitors, damage-associated molecular patterns
- MeSH terms
- Gain of Function Mutation, Animals, Autophagy, DNA, Mitochondrial, Enzyme Inhibitors, Humans, Inflammation, Membrane Proteins, Models, Biological, Models, Molecular, Nucleotides, Cyclic, Nucleotidyltransferases, Signal Transduction, Cell Death, Inflammation Mediators, Adaptor Proteins, Signal Transducing, Cell Proliferation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
