以线粒体代谢物和核酸为目标的抗炎策略

Yukun Min, Luke A. J. O’Neill
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摘要

线粒体代谢物及其衍生物是近年来开发新型抗炎疗法的重点。被广泛使用的治疗药物富马酸二甲酯(DMF)和二甲双胍具有抗炎特性,并已被证明可以靶向代谢。线粒体代谢产物琥珀酸盐、伊他康酸盐和富马酸盐具有多种免疫调节作用,为免疫和炎症疾病的治疗提供了有趣的可能性。线粒体 DNA 和双链 RNA 也被证明具有高度炎症性,可通过特定的模式识别受体(PRR)发挥作用,如线粒体 DNA 受体为 cGAS 和 TLR9,线粒体双链 RNA 受体为 RIG-I、MDA5,线粒体单链 RNA 受体为 TLR7。这些最新发现正在改变我们对线粒体的看法,表明线粒体是多种炎症疾病的核心,并为开发新的抗炎疗法提供了机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting mitochondrial metabolites and nucleic acids as an anti-inflammatory strategy
Mitochondrial metabolites and their derivatives have been the focus of recent efforts to develop new anti-inflammatory therapeutics. The widely used therapeutic agents dimethyl fumarate (DMF) and metformin have anti-inflammatory properties and have been shown to target metabolism. The mitochondrial metabolites succinate, itaconate, and fumarate have multiple immunomodulatory effects and present interesting therapeutic possibilities for immune and inflammatory diseases. Mitochondrial DNA and double-stranded RNA have also been shown to be highly inflammatory, acting via specific pattern recognition receptors (PRRs) such as cGAS and TLR9 for mitochondrial DNA, RIG-I, MDA5 for mitochondrial double stranded RNA, and TLR7 for mitochondrial single stranded RNA. These recent discoveries are changing our view of mitochondria suggesting that they are at the heart of multiple inflammatory diseases and provide opportunities for the development of new anti-inflammatory therapeutics.
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