在多发性硬化症和患者衍生器官中,空间受限的炎症诱导的衰老类质细胞
Francesca Fagiani1, Edoardo Pedrini1, Maria Sofia Martire1,2
1Translational Neuropathology Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Nature communications
|September 26, 2025
概括
多发性硬化症 (MS) 中的慢性炎症可能会加速细胞衰老,特别是在病变内的质细胞中. 这种类似衰老的过程与大脑年龄指标相关,可能是MS治疗的目标.
科学领域:
- 神经免疫学 神经免疫学
- 细胞生物学 细胞生物学
- 神经退行发生神经退行.
背景情况:
- 多发性硬化症 (MS) 中的慢性炎症与渐进的神经衰退有关.
- 细胞衰老在多发性硬化症发病过程中的作用仍然不完全理解.
研究的目的:
- 研究多发性硬化症中未解决的大脑炎症和细胞衰老之间的关联.
- 探索衰老对MS进展的潜在贡献,并确定治疗点.
主要方法:
- 在人类多发性硬化脑组织上单细胞和空间转录学.
- 在人类诱导多能干细胞 (hiPSC) 衍生神经器官中试验诱导衰老.
- 在患者队列 (n=466) 中基于3TMRI的脑年龄估计.
主要成果:
- 在MS白质病变和皮质中观察到类似衰老的质细胞的积累.
- 衰老签名显示了病变核心的空间梯度.
- 微细胞表现出易受炎症诱导衰老的脆弱性,在抗炎药物治疗中部分可逆.
- 增加的大脑年龄与慢性活跃病变的存在相关.
结论:
- 在多发性硬化中未解决的辅酶体炎症可能会导致加速衰老的过程.
- 细胞衰老,特别是微质细胞衰老,可能有助于MS疾病的进展.
- 调节炎症和衰老可能为MS提供治疗策略.
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