New applications of clioquinol in the treatment of inflammation disease by directly targeting arginine 335 of NLRP3
Peipei Chen, Yunshu Wang, Huaiping Tang, Chao Zhou, Zhuo Liu, Shenghan Gao, Tingting Wang, Xu Yun, Sen-Lin Ji
Abstract
) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.
Topics & Concepts
ChemistryClioquinolArginineInflammationDiseasePharmacologyNanotechnologyBiochemistryInternal medicineMedicineMaterials scienceAmino acidInflammasome and immune disordersImmune Response and InflammationGout, Hyperuricemia, Uric Acid