一个可用药物的铜信号通路驱动着炎症
Stéphanie Solier1, Sebastian Müller1, Tatiana Cañeque1
1Equipe Labellisée Ligue Contre le Cancer, Institut Curie, CNRS, INSERM, PSL Research University, Paris, France.
Nature
|April 26, 2023
概括
在线粒体中的铜通过调节细胞代谢和表观遗传学来驱动炎症. 一种名为supformin (LCC-12) 的新药针对这种铜池来减少炎症和重编程细胞状态,
科学领域:
- 免疫学
- 细胞生物学
- 代谢调节
背景情况:
- 炎症是对伤害的重要免疫反应,但在疾病中可能会变得过度.
- 控制炎症反应的精确分子机制尚不完全理解.
- 细胞表面糖蛋白CD44参与免疫和癌症期间的细胞表型调节.
研究的目的:
- 解释炎症反应的分子基础.
- 研究铜在细胞炎症中的作用.
- 开发针对炎症途径的治疗策略.
主要方法:
- 研究了CD44在金属吸收中的作用,特别是铜.
- 在炎症性巨细胞的线粒体中鉴定出反应性铜.
- 分析了NAD (H) 反氧循环的催化及其与过氧化的联系.
- 使用甲胺二聚子 (LCC-12),以准线粒体中的铜.
- 对巨细胞的代谢和表观遗传重编进行了评估.
- 在细菌和病毒感染的小鼠模型中评估LCC-12疗效.
主要成果:
- CD44调节金属的吸收,包括铜.
- 线粒体铜 (II) 催化NAD (H) 反氧循环,促进炎症代谢和表观遗传状态.
- 用LCC-12向线粒体铜减少了NAD (H) 池,反对巨细胞的激活.
- 在体内,LCC-12在减少炎症方面表现出有效性.
结论:
- 铜是细胞可塑性和炎症反应的关键调节剂.
- 针对线粒体铜提供一种新的治疗方法来治疗炎症疾病.
- 代谢重编程和表观遗传控制是治疗炎症的有效策略.
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