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EMBO Mol Med:曲尼斯特可抑制NLRP3炎症小体相关炎症性疾病

2018-03-15 佚名 中国科学技术大学

近日,中国科学技术大学生命科学学院、中国科学院天然免疫与慢性疾病重点实验室和合肥微尺度物质科学国家研究中心周荣斌、江维、张华凤和梁高林研究组与厦门大学邓贤明、中国科大附属第一医院陶金辉研究组合作,发现“老药”曲尼斯特(Tranilast)可通过抑制NLRP3炎症小体改善其驱动的相关炎症性疾病。

近日,中国科学技术大学生命科学学院、中国科学院天然免疫与慢性疾病重点实验室和合肥微尺度物质科学国家研究中心周荣斌、江维、张华凤和梁高林研究组与厦门大学邓贤明、中国科大附属第一医院陶金辉研究组合作,发现“老药”曲尼斯特(Tranilast)可通过抑制NLRP3炎症小体改善其驱动的相关炎症性疾病。

NLRP3炎症小体是由胞内固有免疫受体NLRP3、接头蛋白ASC和蛋白酶caspase-1(半胱氨酸天冬氨酸蛋白酶1)作为核心组成的多蛋白复合物,该复合物组装能够诱导促炎因子IL-1b(白细胞介素1b)和IL-18(白细胞介素18)等的成熟和分泌,从而促进炎症反应发生。NLRP3炎症小体活化与多种人类重大疾病的发生有着密切关系。NLRP3自身突变会导致一类自身炎症性疾病,包括家族性寒冷型自身炎症性综合征(FCAS)、穆-韦二氏综合征(MWS)和慢性幼儿性神经皮肤关节综合征(CINCA)。此外,NLRP3炎症小体能够被高血糖、饱和脂肪酸、胆固醇结晶、尿酸结晶、β-淀粉样蛋白等各种异常代谢产物激活,在2型糖尿病、动脉粥样硬化、痛风、神经退行性疾病、多发性硬化症等疾病的发生中起到重要作用。因此,NLRP3炎症小体是上述疾病重要的候选干预靶点。但目前还没有靶向NLRP3炎症小体的临床药物,靶向NLRP3本身的特异性抑制剂受到极大关注。

曲尼斯特是一种临床抗过敏药物,对哮喘和过敏性皮炎有较好效果和安全性。课题组通过前期筛选和后续研究发现,曲尼斯特可直接结合NLRP3蛋白,通过抑制NLRP3蛋白的多聚,从而抑制后续NLRP3炎症小体组装和活化以及IL-1等炎性细胞因子产生,可在动物模型上有效预防或者治疗穆-韦二氏综合征(MWS)、2型糖尿病和痛风,可抑制痛风病人来源的免疫细胞中炎症小体的活化。该研究发现了曲尼斯特的新型作用靶点,提示其或可用于临床治疗NLRP3相关的炎症性疾病。

相关研究成果发表在EMBO Mol Med上。

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    2018-06-07 最佳损友

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    2018-03-17 yuandd
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    2018-03-17 vera_1207
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