在C9orf72 GGGGCC重复转化为聚合二重复蛋白在FTLD/ALS
Kohji Mori1, Shih-Ming Weng, Thomas Arzberger
1Adolf Butenandt-Institute, Biochemistry, Ludwig-Maximilians University (LMU) Munich, Munich, Germany.
Science (New York, N.Y.)
|February 9, 2013
概括
家庭前叶退化和ALS最常见的遗传原因,C9orf72六核酸重复扩张,导致特定的蛋白质含有. 这些内含物含有二重复蛋白质,直接将遗传突变与观察到的病理联系起来.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 亲属前叶退化和肌缩性侧面硬化 (FTLD/ALS) 通常是由C9orf72六核酸重复扩张引起的.
- 在C9orf72相关的病理中,潜在的病理机制和蛋白质内含的组成仍然在很大程度上是未知的.
研究的目的:
- 为了识别C9orf72病理中发现的特征性细胞内含体内的核心蛋白质.
- 确定C9orf72基因突变与观察到的病态蛋白质聚合物之间的直接联系.
主要方法:
- 在C9orf72六核酸重复扩张的患者样本中分析细胞内含物.
- 使用蛋白质和生化技术,在这些含体内识别蛋白质成分.
主要成果:
- 大多数特征性含有含有多- ((Gly-Ala) 二重复蛋白质.
- 此外,还发现了较少量的聚- ((Gly-Pro) 和聚- ((Gly-Arg) 二重复蛋白.
- 这些二重复蛋白被认为是由于扩展的GGGGCC重复的非ATG启动的翻译而产生的.
结论:
- 这项研究确定了特定的二二重复蛋白质作为C9orf72相关的FTLD/ALS中包含的主要组成部分.
- 这些发现提供了C9orf72基因突变与患者观察到的关键病理特征之间的直接分子联系.
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