与ALS/FTD相关的C9orf72六核酸重复扩张通过多分子G-四重复合形成RNA凝聚物
Federica Raguseo1,2,3, Yiran Wang4,5, Jessica Li4,5
1Imperial College London, Department of Chemistry, Molecular Sciences Research Hub, 82 Wood Lane, London, W12 0BZ, UK.
Nature communications
|December 13, 2023
概括
在ALS/FTD中C9orf72基因扩张形成G-四重复结构. 这些结构驱动无蛋白凝结物的形成,为神经退行性疾病提供潜在的治疗点.
科学领域:
- 分子生物学分子生物学
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
背景情况:
- 肌缩侧面硬化症 (ALS) 和前性痴呆症 (FTD) 是相关的神经退行性疾病.
- 最常见的遗传原因是C9orf72基因的六核酸重复扩张.
研究的目的:
- 在C9orf72重复中研究核酸二次结构的形成.
- 确定这些结构在ALS/FTD中的凝结物生成中的作用.
主要方法:
- 要研究的生物物理技术 (GGGGCC) 没有重复聚合.
- 在人类运动神经元中,G-quadruplex (G4) 选择性光探针染色.
- 在G4展开条件下对凝结物解体的分析.
主要成果:
- 观察到 (GGGGCC) n重复的显著聚合,形成多分子G-四重复合体 (mG4s).
- 在暴露在G4展开条件下,冷凝物被拆解.
- 在C9orf72突变的人类运动神经元中检测到增加的G4结构.
结论:
- 富含G的RNA重复形成由mG4s稳定的无蛋白质凝聚物.
- mG4s对于C9orf72相关的ALS/FTD中的凝结物形成至关重要.
- 这些mG4结构代表了潜在的治疗点.
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