The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Inhibition of double‐strand DNA‐sensing cGAS ameliorates brain injury after ischemic stroke
Open accessAbstract
Cytosolic double-stranded DNA (dsDNA) is a danger signal that is tightly monitored and sensed by nucleic acid-sensing pattern recognition receptors. We study the inflammatory cascade on dsDNA recognition and investigate the neuroprotective effect of cyclic GMP-AMP (cGAMP) synthase (cGAS) antagonist A151 and its mechanisms of neuroprotection in a mouse model of experimental stroke. Here, we found that cerebral ischemia promoted the release of dsDNA into the cytosol, where it initiated inflammatory responses by activating the cGAS. A151 effectively reduced the expression of cGAS, absent in melanoma 2 (AIM2) inflammasome, and pyroptosis-related molecules, including caspase-1, gasdermin D, IL-1β, and IL-18. Furthermore, mice treated with A151 showed a dampened immune response to stroke, with reduced counts of neutrophils, microglia, and microglial production of IL-6 and TNF-α after MCAO. Moreover, A151 administration significantly reduced infarct volume, attenuated neurodeficits, and diminished cell death. Notably, the protective effect of A151 was blocked in a microglia-specific cGAS knockout mouse. These findings offer unique perspectives on stroke pathogenesis and indicate that inhibition of cGAS could attenuate brain inflammatory burden, representing a potential therapeutic opportunity for stroke.
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Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707914 · Cited by 9,482
Reversible middle cerebral artery occlusion without craniectomy in rats.
Longa, E. Z., Weinstein, P. R., Carlson, S., & Cummins, R. (1989) · Stroke · doi:10.1161/01.str.20.1.84 · Cited by 7,463
Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death
Shi, J., Gao, W., & Shao, F. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.10.004 · Cited by 3,088
AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
Hornung, V., Ablasser, A., Charrel-Dennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., & Fitzgerald, K. A. (2009) · Nature · doi:10.1038/nature07725 · Cited by 2,627
The Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436
AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
Fernandes-Alnemri, T., Yu, J.-W., Datta, P., Wu, J., & Alnemri, E. S. (2009) · Nature · doi:10.1038/nature07710 · Cited by 1,831
Ridker, P. M., Thuren, T., Zalewski, A., & Libby, P. (2011) · American Heart Journal · doi:10.1016/j.ahj.2011.06.012 · Cited by 799
cGAS is essential for the antitumor effect of immune checkpoint blockade
Wang, H., Hu, S., Chen, X., Shi, H., Chen, C., Sun, L., & Chen, Z. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621363114 · Cited by 563
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The AIM 2 inflammasome: Sensor of pathogens and cellular perturbations
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Cited by
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
Pyroptosis in inflammatory diseases and cancer
Rao, Z., Zhu, Y., Yang, P., Chen, Z., Xia, Y., Qiao, C., Liu, W., Deng, H., Li, J., Ning, P., et al. (2022) · Theranostics · doi:10.7150/thno.71086 · Cited by 800
Inflammatory Responses After Ischemic Stroke
DeLong, J. H., Ohashi, S. N., O’Connor, K. C., & Sansing, L. H. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00943-7 · Cited by 319
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
Accumulation of polystyrene microplastics induces liver fibrosis by activating cGAS/STING pathway
Shen, R., Yang, K., Cheng, X., Guo, C., Xing, X., Sun, H., Liu, D., Liu, X., & Wang, D. (2022) · Environmental Pollution · doi:10.1016/j.envpol.2022.118986 · Cited by 264
Metadata
- Authors
- Li, Q., Cao, Y., Dang, C., Han, B., Han, R., Ma, H., Hao, J., & Wang, L.
- Venue
- EMBO Molecular Medicine
- Published
- 2020-04
- Volume
- 12
- Issue
- 4
- Pages
- e11002-e11002
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- OpenAlex
- W3014630476
- Cited by
- 273
- References
- 13
- FWCI
- 11.80
- Type
- journal article
- Language
- en
- Open access
- gold
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- Li, Q., Cao, Y., Dang, C., Han, B., Han, R., Ma, H., Hao, J., & Wang, L. (2020). Inhibition of double‐strand DNA‐sensing cGAS ameliorates brain injury after ischemic stroke. EMBO Molecular Medicine. https://doi.org/10.15252/emmm.201911002
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