磷酸化在NLRP3炎症小体活化中的调控作用

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NLRP3是位于细胞质中的模式识别受体,属于NOD样受体家族.在多种危险相关分子模式和病原体相关分子模式的激活下,NLRP3受体通过招募接头蛋白ASC和半胱氨酸蛋白酶原caspase-1形成一个多聚蛋白复合物,称之为NLRP3炎症小体.NLRP3炎症小体的主要功能是通过促进免疫应答清除病原微生物和危险信号,维持体内平衡.但是,NLRP3炎症小体异常活化又会引发多种炎症性疾病.因此,其活化必须受到严格调控.近期,多种激酶和磷酸酶被报道调控NLRP3炎性小体活化,这表明磷酸化在调控炎症小体活化中起着至关重要的作用.在本文中,我们概述了多种激酶和磷酸酶如何调控NLRP3炎症小体活化,并概述了磷酸化在NLRP3炎症小体活化中的调控作用.此外,我们还总结了靶向NLRP3相关激酶或磷酸酶治疗炎症小体相关疾病的潜在药用化合物.“,”NLRP3 is a pattern recognition receptor localized in the cytoplasm that belongs to the NOD-like receptor family. Upon activation by a wide range of danger-associated molecular patterns ( DAMPs) and pathogen-associated molecular patterns ( PAMPs) , NLRP3 recruits the adaptor protein ASC and the cysteine protease pro-caspase-1 to form a multiprotein complex called the NLRP3 inflammasome. The primary function of the NLRP3 inflammasome is to maintain homeostasis by facilitating the immune response to remove pathogens and danger signals. However, aberrant activation of the NLRP3 inflammasome also causes a variety of inflammatory diseases. Therefore, NLRP3 inflammasome activation must be precisely regulated. Recently, various kinases and phosphatases have been reported to control the NLRP3 inflammasome activation, suggesting that phosphorylation plays a vital role in regulating the inflammasome activation. In this review, we summarize how various kinases and phosphatases control the NLRP3 inflammasome activation and provide an overview of the regulatory role of phosphorylation in the NLRP3 inflammasome activation. Further, we discuss the potential pharmacologically compounds that target NLRP3-related kinases or phosphatases for the treatment of inflammasome-driven diseases.
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