在再生肌肉中,TDP-43和RNA形成粉样肌粒
Thomas O Vogler1,2, Joshua R Wheeler2,3, Eric D Nguyen2,4
1Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO, USA.
Nature
|November 23, 2018
概括
在神经肌肉疾病中,TDP-43蛋白质的细胞质聚合物很常见. 研究人员发现,正常的肌肉再生涉及TDP-43形成临时的"肌肉颗粒",如果不清除,可能导致疾病聚合物.
科学领域:
- 生物化学
- 分子生物学
- 神经科学
背景情况:
- 细胞质聚合TDP-43是神经肌肉疾病的标志,如ALS和包容体肌病.
- 虽然TARDBP突变导致一些TDP-43聚合,但大多数患者具有野生型TDP-43聚合物,这表明存在未知的机制.
研究的目的:
- 研究神经肌肉疾病中野生型TDP-43聚合背后的机制.
- 探索TDP-43在骨肌肉中的正常功能及其在疾病发病过程中的潜在作用.
主要方法:
- 研究了TDP-43在老鼠和人类模型的骨肌肉再生中的作用.
- 含有TDP-43的细胞质组件 (肌体颗粒) 的特征
- 评估了肌粒形成,mRNA结合,清除和粉样纤维的潜力.
主要成果:
- TDP-43对于骨肌肉的形成至关重要,并在再生过程中形成短暂的粉样"肌粒".
- 这些肌体颗粒将mRNA与sarcomeric蛋白结合,并在肌肉成熟时被清除.
- 肌肉颗粒可以在体外播种TDP-43粉状纤维,并且在包括体肌肉病的小鼠模型中升高.
结论:
- 在肌肉再生过程中,肌肉颗粒代表了TDP-43的正常,短暂的组合.
- 在常见的神经肌肉疾病中,肌粒组合或清除的失调可能是有毒TDP-43聚合物的主要来源.
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