在髓状细胞中的C9orf72可以防止对微生物糖原的炎症反应
Blake McCourt1, Katelyn Lemr2, Shinjon Chakrabarti1
1Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Cell reports
|January 25, 2026
概括
肠道中的细菌糖原通过激活C9orf72通路,促进了肌缩侧面硬化症 (ALS) 中的炎症和神经退行. 改变肠道糖原水平可能为ALS提供治疗策略.
科学领域:
- 神经免疫学 神经免疫学
- 微生物组研究 微生物组研究
- 神经退行性疾病 神经退行性疾病
背景情况:
- 肌缩侧面硬化症 (ALS) 与肠道失调和神经炎症有关.
- 肠道细菌和ALS遗传因素之间的相互作用,如C9ORF72突变,尚未完全理解.
研究的目的:
- 研究肠道共生物如何与ALS.中的C9ORF72突变相互作用.
- 确定导致ALS神经退行的细菌机制.
主要方法:
- 已确定促进C9ORF72依赖性细胞因子释放的细菌菌株.
- 利用元转录组学来分析炎症途径.
- 用特定的细菌殖民无菌小鼠,并评估神经结果.
- 分析了人类便样本,以检测细菌糖原的存在.
主要成果:
- 发现10种细菌菌株以C9orf72依赖的方式诱导细胞因子的释放.
- 细菌糖原生物合成途径与驱动炎症有关.
- 被炎症性糖原生成细菌殖民的小鼠表现出增加的单细胞化,血脑屏障破坏和神经炎症.
- 酶性糖原消化改善了小鼠的生存率,并减少了小鼠的大脑炎症.
- 在大多数ALS患者的便样本中检测到炎症性细菌糖原.
结论:
- 细菌葡萄糖原作为关键调解者,将肠道失调与ALS中神经炎症联系起来.
- 准细菌糖原为ALS和相关的C9ORF72相关疾病提供了潜在的治疗途径.
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