通过cPLA2-MAVS对星细胞致病活性进行代谢控制
Chun-Cheih Chao1, Cristina Gutiérrez-Vázquez1, Veit Rothhammer2
1Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cell
|December 10, 2019
概括
星球细胞中的脂代谢通过激活细胞酶A2 (cPLA2) 和线粒体抗病毒信号蛋白 (MAVS) 来驱动中枢神经系统 (CNS) 的炎症. 一种名为Miglustat的药物可以抑制这些炎症途径.
科学领域:
- 神经免疫学
- 代谢途径
- 天体细胞生物学
背景情况:
- 代谢影响周围免疫,但其在中枢神经系统 (CNS) 炎症中的作用尚不清楚.
- 星球细胞在中枢神经系统的平衡和疾病中起着至关重要的作用.
研究的目的:
- 研究脂代谢在星体介导的中枢神经系统炎症中的作用.
- 确定将新陈代谢与神经炎症联系起来的分子机制.
主要方法:
- 蛋白质组,代谢组和转录组分析.
- 在实验性自身免疫脑炎 (EAE) 模型中进行乱研究.
- 研究了涉及cPLA2,MAVS和HK2的蛋白质相互作用.
主要成果:
- 星球细胞中的脂代谢激活cPLA2-MAVS相互作用,促进NF-κB驱动的中枢神经系统炎症.
- 这种相互作用破坏了MAVS-HK2结合,减少了乳酸的产生和神经元的支持.
- 一种现有的药物Miglustat抑制了致病性星球细胞活动,并降低了EAE的严重程度.
结论:
- 确定了导致中枢神经系统炎症的新型免疫代谢途径.
- 发现了MAVS在神经炎症中的新作用.
- 在中枢神经系统的炎症性疾病中,Miglustat具有治疗潜力.
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