中国科学家发现绿茶提取物EGCG可抑制cGAS激活
Published:19 Dec.2018    Source:http://www.cncbd.org.cn/News/Detail/8033

2018年12月3日,来自国家生物医学分析中心张学敏院士课题组与李涛课题组合作在Nature Immunology上发表了题为G3BP1 promotes DNA binding and activation of cGAS的研究论文,发现了一个新的cGAS(cyclic GMP-AMP synthase,环鸟苷酸-腺苷酸合成酶)调控因子G3BP1(GTPase-activating protein-(SH3domain)-binding protein 1),G3BP1具有核酸结合能力,在细胞抗病毒免疫特别是抗RNA病毒免疫中具有重要作用。他们还发现一种来自绿茶的天然小分子化合物EGCG(Epigallocatechin gallate,表没食子儿茶素没食子酸酯)可以抑制G3BP1与cGAS的结合,从而抑制cGAS激活。此外,研究者还利用自身免疫动物模型以及AGS病人( Aicardi–Goutières syndrome,一种遗传性脑病,其特征是获得性小头畸形、基底节钙化、脑白质营养不良、脑萎缩、伴脑脊液淋巴细胞慢性增多和α-干扰素增高等)的细胞验证了EGCG在体内抑制cGAS的有效性。该工作为AGS综合征等目前尚缺乏治疗手段的自身免疫性疾病提供了治疗策略选择。

 

cGAS-STING通路与许多疾病的发生密切相关,近年来围绕cGAS-STING通路开发抑制剂或者激动剂研究非常火热,最近的相关研究报道也是层出不穷。2012年底,美国西南医学中心华人科学家陈志坚课题组首次鉴定出了天然免疫领域具有里程碑意义的DNA识别受体cGAS。cGAS能直接检测细胞质DNA并通过下游关键蛋白STING(同MITA,2008年由武汉大学舒红兵院士率先发现)、IRF3最终激活下游I型干扰素信号。今年7月份,Nature发文报道了STING的新型小分子抑制剂;11月初Nature上报道了STING的激动剂diABZI,通过激活STING则可有效释放T细胞并摧毁癌细胞,显示出在肿瘤免疫治疗中的巨大潜力。

 

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