The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
cGAS drives noncanonical-inflammasome activation in age-related macular degeneration
Open accessAbstract
Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D–dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness.
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.
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
Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death
Shi, J., Zhao, Y., Wang, K., Shi, X., Wang, Y., Huang, H., Zhuang, Y., Cai, T., Wang, F., & Shao, F. (2015) · Nature · doi:10.1038/nature15514 · Cited by 6,659
Wong, W. L., Su, X., Li, X., Cheung, C. M. G., Klein, R., Cheng, C.-Y., & Wong, T. Y. (2014) · The Lancet Global Health · doi:10.1016/s2214-109x(13)70145-1 · Cited by 5,331
Cyclic 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
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844
Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
Kayagaki, N., Stowe, I. B., Lee, B. L., O’Rourke, K., Anderson, K., Warming, S., Cuellar, T., Haley, B., Roose-Girma, M., Phung, Q. T., et al. (2015) · Nature · doi:10.1038/nature15541 · Cited by 3,686
Mitochondria: In Sickness and in Health
Nunnari, J., & Suomalainen, A. (2012) · Cell · doi:10.1016/j.cell.2012.02.035 · Cited by 3,479
Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
Liu, X., Zhang, Z., Ruan, J., Pan, Y., Magupalli, V. G., Wu, H., & Lieberman, J. (2016) · Nature · doi:10.1038/nature18629 · Cited by 3,202
Nakahira, K., Haspel, J. A., Rathinam, V. A. K., Lee, S.-J., Dolinay, T., Lam, H. C., Englert, J. A., Rabinovitch, M., Cernadas, M., Kim, H. P., et al. (2011) · Nature Immunology · doi:10.1038/ni.1980 · Cited by 3,049
Self-citationOxidized arachidonic and adrenic PEs navigate cells to ferroptosis
Kagan, V. E., Mao, G., Qu, F., Angeli, J. P. F., Doll, S., Croix, C. S., Dar, H. H., Liu, B., Tyurin, V. A., Ritov, V. B., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2238 · Cited by 3,029
Non-canonical inflammasome activation targets caspase-11
Kayagaki, N., Warming, S., Lamkanfi, M., Walle, L. V., Louie, S., Dong, J., Newton, K., Qu, Y., Liu, J., Heldens, S., et al. (2011) · Nature · doi:10.1038/nature10558 · Cited by 2,530
Cited by
The NLRP3 inflammasome: molecular activation and regulation to therapeutics
Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884
The cGAS–STING pathway as a therapeutic target in inflammatory diseases
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00524-z · Cited by 2,309
Molecular mechanisms and cellular functions of cGAS–STING signalling
Hopfner, K.-P., & Hornung, V. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0244-x · Cited by 2,052
DAMP-sensing receptors in sterile inflammation and inflammatory diseases
Gong, T., Liu, L., Jiang, W., & Zhou, R. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0215-7 · Cited by 1,672
DNA sensing by the cGAS–STING pathway in health and disease
Motwani, M., Pesiridis, S., & Fitzgerald, K. A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0151-1 · Cited by 1,467
Self-citationThe cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer
Li, T., & Chen, Z. J. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180139 · Cited by 1,293
Targeting STING with covalent small-molecule inhibitors
Haag, S. M., Gulen, M. F., Reymond, L., Gibelin, A., Abrami, L., Decout, A., Heymann, M., van der Goot, F. G., Turcatti, G., Behrendt, R., et al. (2018) · Nature · doi:10.1038/s41586-018-0287-8 · Cited by 1,178
cGAS in action: Expanding roles in immunity and inflammation
Ablasser, A., & Chen, Z. J. (2019) · Science · doi:10.1126/science.aat8657 · Cited by 1,077
The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates
Franceschi, C., Garagnani, P., Morsiani, C., Conte, M., Santoro, A., Grignolio, A., Monti, D., Capri, M., & Salvioli, S. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00061 · Cited by 945
Mitochondrial Damage Causes Inflammation via cGAS-STING Signaling in Acute Kidney Injury
Maekawa, H., Inoue, T., Ouchi, H., Jao, T.-M., Inoue, R., Nishi, H., Fujii, R., Ishidate, F., Tanaka, T., Tanaka, Y., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.050 · Cited by 586
Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration
Kaarniranta, K., Uusitalo, H., Blasiak, J., Felszeghy, S., Kannan, R., Kauppinen, A., Salminen, A., Sinha, D., & Ferrington, D. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100858 · Cited by 526
PINK1/PARKIN signalling in neurodegeneration and neuroinflammation
Quinn, P. M. J., Moreira, P. I., Ambrósio, A. F., & Alves, C. H. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01062-w · Cited by 481
The ageing epigenome and its rejuvenation
Zhang, W., Qu, J., Liu, G.-H., & Belmonte, J. C. I. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0204-5 · Cited by 458
Zhang, W., Li, G., Luo, R., Lei, J., Song, Y., Wang, B., Ma, L., Liao, Z., Ke, W., Liu, H., et al. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00729-9 · Cited by 325
Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response
Wan, D., Jiang, W., & Hao, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00615 · Cited by 270
Cytosolic DNA sensing by cGAS: regulation, function, and human diseases
Yu, L., & Liu, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00554-y · Cited by 269
Bucher, K., Rodríguez-Bocanegra, E., Dauletbekov, D., & Fischer, M. D. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100915 · Cited by 242
Jin, W.-N., Shi, K., He, W., Sun, J.-H., Van Kaer, L., Shi, F.-D., & Liu, Q. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00745-w · Cited by 179
Pharmacological modulation of nucleic acid sensors - therapeutic potential and persisting obstacles
Vanpouille-Box, C., Hoffmann, J. A., & Galluzzi, L. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0043-2 · Cited by 183
Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease
Sharma, M., Rajendrarao, S., Shahani, N., Ramírez-Jarquín, U. N., & Subramaniam, S. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002144117 · Cited by 155
Zou, M., Ke, Q., Nie, Q., Qi, R., Zhu, X., Liu, W., Hu, X., Sun, Q., Fu, J.-L., Tang, X., et al. (2022) · Cell Death & Differentiation · doi:10.1038/s41418-022-00967-4 · Cited by 138
Innate Immune Response in Retinal Homeostasis and Inflammatory Disorders
Murakami, Y., Ishikawa, K., Nakao, S., & Sonoda, K.-H. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100778 · Cited by 125
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
Fukuda, S., Varshney, A., Fowler, B. J., Wang, S.-B., Narendran, S., Ambati, K., Yasuma, T., Magagnoli, J., Leung, H., Hirahara, S., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2022751118 · Cited by 65
Self-citationAmbati, J., Magagnoli, J., Leung, H., Wang, S.-B., Andrews, C. A., Fu, D., Pandey, A., Sahu, S., Narendran, S., Hirahara, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18528-z · Cited by 66
Self-citationThe learning curve of murine subretinal injection among clinically trained ophthalmic surgeons
Huang, P., Narendran, S., Pereira, F., Fukuda, S., Nagasaka, Y., Apicella, I., Yerramothu, P., Marion, K. M., Cai, X., Sadda, S. R., et al. (2022) · Translational Vision Science & Technology · doi:10.1167/tvst.11.3.13 · Cited by 10
Self-citation
Metadata
- Authors
- Kerur, N., Fukuda, S., Banerjee, D., Kim, Y., Fu, D., Apicella, I., Varshney, A., Yasuma, R., Fowler, B. J., Baghdasaryan, E., Marion, K. M., Huang, X., Yasuma, T., Hirano, Y., Serbulea, V., Ambati, M., Ambati, V. L., Kajiwara, Y., Ambati, K., Hirahara, S., Bastos-Carvalho, A., Ogura, Y., Terasaki, H., Oshika, T., Kim, K. B., Hinton, D. R., Leitinger, N., Cambier, J. C., Buxbaum, J. D., Kenney, M. C., Jazwinski, S. M., Nagai, H., Hara, I., West, A. P., Fitzgerald, K. A., Sadda, S. R., Gelfand, B. D., & Ambati, J.
- Venue
- Nature Medicine
- Published
- 2017-11-27
- Volume
- 24
- Issue
- 1
- Pages
- 50-61
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2768387192
- Cited by
- 286
- References
- 78
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- green
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
