在神经管缺陷中,PCSK9功能丧失通过LIN28A/HES5/JMY轴扰乱了细胞微纤维网络
Xiaoshuai Li1,2, Rui Wang3, Wenting Luo1
1NHC Key Laboratory of Congenital Malformation, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|August 11, 2025
概括
神经管缺陷 (NTD) 与PCSK9损失有关,影响胎儿发育. 这项研究揭示了PCSK9通过LIN28A/HES5/JMY通路在神经发育中的作用,为NTD提供了新的治疗点.
科学领域:
- 发展生物学 发展生物学
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
背景情况:
- 神经管缺陷 (NTD) 是一种严重的先天性形,影响中枢神经系统.
- PCSK9是已知的NTD产前诊断标志物,但其致病作用尚不清楚.
研究的目的:
- 阐明PCSK9在神经管发育和NTD病变发生过程中的作用.
- 为了确定PCSK9影响神经发育的分子机制.
主要方法:
- 在神经器官 (NO) 和神经原生细胞 (NPC) 模型中利用了PCSK9淘汰胚胎干细胞 (ESC).
- 进行了转录组测序和斑马鱼模型实验.
- 研究了PCSK9,LIN28A,HES5和JMY之间的相互作用.
主要成果:
- PCSK9的损失导致了NO中神经管结构不完整和NPC中微纤维障碍.
- 通过JMY分子,PCSK9缺乏导致NTD,斑马鱼研究证实了这一点.
- PCSK9充当分子伴侣,促进LIN28A降解,通过HES5.5影响JMY表达.
结论:
- 通过LIN28A/HES5/JMY通路,PCSK9的损失会破坏细胞微纤维网络,导致NTD.
- 这些发现为NTD病原和潜在的治疗策略提供了关键的见解.
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