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In ischemic stroke, the inflammatory response triggered by innate immunity is crucial, with the role of Receptor-interacting kinase 2 (RIP2) still needing to be fully understood. The study on cell models revealed elevated RIP2 and OTUD1 levels in affected brain cells. Inhibiting RIP2 with GSK559 improved outcomes by suppressing NF-κB activity and inflammation. Mechanistically, OTUD1 interacted with RIP2, removing its K63-linked polyubiquitin chains and inhibiting NF-κB activation. OTUD1 deficiency worsened ischemic injury. The findings suggest RIP2 mediates ischemic damage through inflammation, while OTUD1 mitigates brain injury by inhibiting RIP2-induced NF-κB activation.
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