NCoR1:一个关键的参与者,调节了mycobacterium结核病的发病过程
Kaushik Sen1,2, Viplov Kumar Biswas1,3, Arup Ghosh1,3
1Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), Bhubaneswar, Odisha, India.
通过AMPK-MTOR-TFEB通路破坏自和溶酶体功能,NCOR1的枯竭会损害宿主对Mycobacterium tuberculosis (Mtb) 的防御能力. 恢复NCOR1或使用特定的治疗方法可以增强Mtb清除.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 结核菌 (Mtb) 逃避宿主防御,包括自和溶酶体功能.
- 转录性共抑制剂NCOR1参与各种细胞过程,但其在Mtb病变发生过程中的作用尚不清楚.
研究的目的:
- 研究NCOR1在调节自,溶酶体生物发生和Mtb病变发生中的作用.
- 探索针对宿主导治疗中针对NCOR1的治疗潜力,以对抗Mtb.
主要方法:
- 宿主细胞中NCOR1的耗尽.
- 分析AMPK-MTOR-TFEB信号轴及其对自和溶酶体生物发生的影响.
- 用拉帕米辛,抗菌素A或甲福林治疗NCOR1枯竭细胞.
- 在宿主细胞中评估Mtb生存和清除.
主要成果:
- NCOR1 枯竭会破坏 AMPK-MTOR-TFEB 途径,损害自和溶酶体生物发生,从而增加 Mtb 存活率.
- 恢复TFEB活动和自流量 (LC3-II水平) 是通过对NCOR1贫乏细胞用拉巴胺素,抗菌素A或甲胺进行治疗而实现的.
- 外源NCOR1表达拯救了信号轴和自机械.
结论:
- 通过调节自和 lysosome 功能,NCOR1 在宿主防御 Mtb 中起着至关重要的作用.
- 准NCOR1或调节AMPK-MTOR-TFEB通路为针对结核病的新型宿主导疗法提供了一个有希望的策略.
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