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.
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“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]
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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]
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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]
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Citations
Cites
3 retracted
Items 201–212 of 212
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SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibilityPreprint
Zhou, B., Thao, T. T. N., Hoffmann, D., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.27.357558 · Cited by 59
Huffman, B. J., Chen, S., Schwarz, J. L., Plata, R. E., Chin, E. N., Lairson, L. L., Houk, K. N., & Shenvi, R. A. (2020) · Nature Chemistry · doi:10.1038/s41557-019-0413-8 · Cited by 52
Siedel, H., Roers, A., Rösen‐Wolff, A., & Luksch, H. (2020) · Clinical Immunology · doi:10.1016/j.clim.2020.108466 · Cited by 45
Bennion, B. G., Croft, C. A., Ai, T. L., Qian, W. P., Menos, A. M., Miner, C. A., Frémond, M., Doisne, J., Andhey, P. S., Platt, D. J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107771 · Cited by 35
A defect in COPI-mediated transport of STING causes immune dysregulation in COPA syndromePreprint
Deng, Z., Chong, Z., Law, C. S., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.20.106500 · Cited by 21
Comment on “The Common R71H-G230A-R293Q Human TMEM173 Is a Null Allele”
Sivick, K. E., Surh, N. H., Desbien, A. L., Grewal, E. P., Katibah, G. E., McWhirter, S. M., & Dubensky, T. W. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700294 · Cited by 19
Activation of STING due to COPI-deficiencyPreprint
Steiner, A., Hrovat-Schaale, K., Prigione, I., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.09.194399 · Cited by 18
Homeostatic regulation of STING by Golgi-to-ER membrane trafficPreprint
Mukai, K., Ogawa, E., Uematsu, R., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.20.107664 · Cited by 16
TBK1 and IKK epsilon Act Redundantly to Mediate STING-Induced NF-kappa B Responses in Myeloid Cells
Balka, K. R., Louis, C., Saunders, T. L., Smith, A. M., Calleja, D. J., D’Silva, D. B., Moghaddas, F., Tailler, M., Lawlor, K. E., Zhan, Y., et al. (2020) · Cell Reports · Cited by 12
Lahey, L. J., Wen, X., Mardjuki, R. E., Böhnert, V., Hess, G. T., Ritchie, C., Carozza, J. A., Maduke, M. C., Bassik, M. C., & Li, L. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.13.948273 · Cited by 9
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
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
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