AI Article Synopsis
- - Type I interferon (IFN) is linked to autoimmune diseases like lupus and rare disorders such as Aicardi-Goutières syndrome, where a new DNA-activated pathway involving the enzyme cGAS has been identified.
- - Researchers conducted an in silico screening of drug libraries to find compounds that could inhibit cGAS activity, focusing on antimalarial drugs (AMDs) that might interact with the cGAS/dsDNA complex.
- - The study found that certain AMDs effectively reduced IFN-β production by blocking stimulation of cGAS, suggesting that these drugs could offer new treatment options for conditions related to type I IFNs and cGAS activation.
Article Abstract
Type I IFN is strongly implicated in the pathogenesis of systemic autoimmune diseases, such as lupus, and rare monogenic IFNopathies, including Aicardi-Goutières syndrome. Recently, a new DNA-activated pathway involving the enzyme cyclic GMP-AMP synthase (cGAS) was described and potentially linked to Aicardi-Goutières syndrome. To identify drugs that could potentially inhibit cGAS activity, we performed in silico screening of drug libraries. By computational analysis, we identified several antimalarial drugs (AMDs) that were predicted to interact with the cGAS/dsDNA complex. Our studies validated that several AMDs were effective inhibitors of IFN-β production and that they functioned by inhibiting dsDNA stimulation of cGAS. Because AMDs have been widely used in human diseases and have an excellent safety profile, our findings suggest new therapeutic strategies for the treatment of severe debilitating diseases associated with type I IFNs due to cGAS activation.
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| http://dx.doi.org/10.4049/jimmunol.1402793 | DOI Listing |
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