在外周神经系统的Ranvier节点中缺少补膜调节蛋白
Netanel Karbian1, Yael Eshed-Eisenbach2,3, Marian Zeibak1
1Rheumatology and Rare Disease Research Center, The Wohl Institute for Translational Medicine, Hadassah-Hebrew University Medical Center and School of Medicine, Jerusalem, Israel.
Journal of neuroinflammation
|October 24, 2023
概括
兰维尔节点中缺少CD59 (补充衰变加速因子),使他们容易受到补充攻击. 这一发现解释了吉-巴雷综合征 (GBS) 和CD59缺乏症中的脱髓化.
科学领域:
- 神经免疫学 神经免疫学
- 补充系统生物学 补充系统生物学
背景情况:
- 缺少CD59会导致神经病变,血液溶解性贫血和中风,其中17/18名患者患有复发的吉林巴雷综合征 (GBS).
- 在周围神经系统 (PNS) 中补充调节者的作用仍然不清楚.
研究的目的:
- 调查补充调节器的局部化和功能,特别是CD59,在人类和小鼠PNS中.
- 为了确定兰维埃结节和髓结节对补充介导损伤的易感性.
主要方法:
- 通过共聚焦和电子显微镜检查了人类和小鼠外周神经中的补体调节器定位.
- 从野生类型和CD59a缺乏的小鼠中分析了坐骨神经和背部根 (DRG) 神经元/施万细胞培养物.
主要成果:
- 缺乏CD59a的小鼠表现出正常的神经形态,但随着年龄的增长而发展出髓异常.
- 在健康神经的内部节点沿线发现了CD59,但在Ranvier节点中缺席.
- 兰维尔节点缺乏其他补充调节器 (CD46,CD55,CD35,Crry),增加了脆弱性.
结论:
- 由于CD59缺失,Ranvier的节点不受补体末端攻击的保护.
- 人类PNS髓受CD59和CD55的保护,但Ranvier的节点是脆弱的.
- 这种脆弱性有助于GBS和CD59缺乏的脱髓化.
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