髓损伤之前的轴突损伤和多发性硬化症的症状发作
Ahmed Abdelhak1, Gabriel Cerono2, Fahime Sheikhzadeh3
1Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, CA, USA. ahmed.abdelhak@ucsf.edu.
Nature medicine
|October 20, 2025
概括
多发性硬化症 (MS) 在症状出现前几年就会出现髓损伤,其次是轴突损伤. 早期的蛋白质变化表明涉及到特定的途径,可能有助于早期发现MS.
科学领域:
- 神经免疫学 神经免疫学
- 蛋白质组学是指蛋白质组学.
- 生物标志物发现发现
背景情况:
- 多发性硬化症 (MS) 生物发病的确切时间尚不清楚.
- 识别早期的病理事件对于了解多发性硬化症的进展和制定干预措施至关重要.
研究的目的:
- 使用先进的蛋白质组学来定义MS的生物神经发作.
- 描述表征前的MS背后的分子机制.
- 为了确定早期发现多发性硬化症的潜在生物标志物.
主要方法:
- 在前症状多发性硬化症患者的血清样本上使用高通量发现蛋白质组学,并与健康对照匹配.
- 分析了蛋白质组的变化,以确定群体之间的分子差异.
- 研究了髓损伤,轴突损伤和星球细胞参与之间的时间关系.
主要成果:
- 在症状出现前大约7年检测到髓损伤的证据,轴突损伤前大约1年.
- 只有在MS的临床发病时才观察到星球细胞的参与.
- 血清蛋白质组的显著变化表明,在症状前阶段,互白素-3和核因子kappa B通路的参与.
- 在一些多发性硬化症患者中,明显的自身抗体特征与免疫细胞活性增加相关.
结论:
- 在MS中,髓损伤比轴突损伤和临床症状早几年.
- 特定的蛋白质通路改变在MS的前症状阶段是显而易见的.
- 拟议的蛋白质生物标志物小组可能有助于将症状前多发性硬化与健康对照区分开来,需要进一步验证.
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