In autoimmune diseases, the immune system turns against the body instead of protecting it. Aicardi-Goutieres Syndrome (AGS) is a rare genetic disorder that mainly affects the brain, while systemic lupus erythematosus (SLE) can affect the skin, joints, kidneys, brain and other organs. Neither disease has a cure, and treatments can control symptoms. Researchers at the UT Southwestern Medical Center have identified an enzyme as a major culprit of these two autoimmune diseases.
An enzyme, called cGAS, sounds an alarm for the body's innate immune system. The research team observed that activating this enzyme causes AGS and SLE in mice, while inhibiting the same enzyme rescues them.
‘Researchers at the UT Southwestern Medical Center have identified an enzyme as a major culprit of Aicardi-Goutieres Syndrome and systemic lupus erythematosus. Activating the cGAS enzyme causes AGS and SLE in mice, while inhibiting the same enzyme rescues them.’
AdvertisementSenior author Dr. Zhijian James Chen said, "These results suggest that inhibition of the enzyme cGAS may be an effective therapy for autoimmune diseases such as AGS and SLE, which are linked to the same inflammatory pathway. cGAS is likely amenable to inhibition by small-molecule drugs and that the recent determination of the high-resolution structures of cGAS should facilitate development of such inhibitors."
The research team also studied mice genetically engineered to lack a DNA-digesting enzyme called DNase-II. The researchers said, "While the resulting inability to degrade lysosomal DNA led to lethal autoimmunity, once again cGAS inhibition rescued the mice."
The study is published in the Proceedings of the National Academy of Sciences (PNAS).
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