Sensing of cytosolic DNA by cyclic GMP–AMP synthase (cGAS) is central to the pathogenesis of a number of autoinflammatory syndromes and possibly some autoimmune diseases, such as systemic lupus erythematosus (SLE). Activation of cGAS signalling requires its deacetylation, so might aspirin have therapeutic potential to treat SLE by acetylating cGAS?
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References
Amann, R. & Peskar, B. A. Anti-inflammatory effects of aspirin and sodium salicylate. Eur. J. Pharmacol. 447, 1–9 (2002).
Dai, J. et al. Acetylation blocks cGAS activity and inhibits self-DNA-induced autoimmunity. Cell 176, 1447–1460 (2019).
Ronnblom, L. & Eloranta, M. L. The interferon signature in autoimmune diseases. Curr. Opin. Rheumatol. 25, 248–253 (2013).
Crow, Y. J. et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am. J. Med. Genet. A 167A, 296–312 (2015).
Ablasser, A. & Chen, Z. J. cGAS in action: Expanding roles in immunity and inflammation. Science 363, doi:10.1126/science.aat8657 (2019).
Henry, D. et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. BMJ 312, 1563–1566 (1996).
Morita, M. et al. Gene-targeted mice lacking the Trex1 (DNase III) 3′→5′ DNA exonuclease develop inflammatory myocarditis. Mol. Cell. Biol. 24, 6719–6727 (2004).
Jastreboff, P. J. et al. Differential uptake of salicylate in serum, cerebrospinal fluid, and perilymph. Arch. Otolaryngol. Head Neck Surg. 112, 1050–1053 (1986).
An, J. et al. cGAMP and cGAS are expressed in a subset of patients with systemic lupus erythematosus and associate with disease activity. Arthritis Rheum. 69, 800–807 (2017).
An, J. et al. Anti-malarial drugs as immune modulators: new mechanisms for old drugs. Annu. Rev. Med. 68, 317–330 (2016).
Acknowledgements
The author thanks J. An and Y. Lin for helpful discussions. The author also notes that his work is supported by grants from the Lupus Research Alliance.
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The author declares that he is a co-founder of Amdax Therapeutics, and a consultant for BellBrook Labs.
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Elkon, K.B. Aspirin meets cGAS. Nat Rev Rheumatol 15, 254–255 (2019). https://doi.org/10.1038/s41584-019-0205-y
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DOI: https://doi.org/10.1038/s41584-019-0205-y
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