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阿尔茨海默病的病原遗传进展与调节保留的内子的变化和循环RNAs的编辑有关
Karol Andrea Arizaca Maquera1, Justin Ralph Welden2, Giorgi Margvelani1
1Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, United States.
Frontiers in molecular neuroscience
|June 2, 2023
概括
在阿尔茨海默病 (AD) 进展过程中,循环RNA (circRNAs) 和RNA编辑增加. 新的翻译circRNAs可能在阿尔茨海默病的发展中发挥作用,为疾病机制提供了新的见解.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 阿尔茨海默氏病 (AD) 的进展涉及不太了解的分子变化.
- 由微管相关蛋白tau (MAPT) 组成的神经纤维状结 (NFT) 是阿尔茨海默病的标志,从内腔皮层扩散.
研究的目的:
- 在阿尔茨海默病 (AD) 进展过程中调查信使RNA (mRNA) 和循环RNA (circRNA) 的变化.
- 为了将这些变化与布拉克神经纤维状 (NFT) 阶段相关联.
主要方法:
- 在Braak NFT I-VI阶段对人类大脑样本进行RNA测序 (纳米孔和Illumina).
- 使用RNase R处理和生物信息工具分析circRNAs.
- 转染实验用于分析circRNA表达结构.
主要成果:
- 确定了11873个circRNAs,其中276个与Braak NFT阶段显著相关.
- 在AD进展期间,在circRNAs中观察到腺到 inosine RNA编辑的三倍增加,与mRNAs没有看到这种相关性.
- CircMAN2A1表达与AD进展相关,RNA编辑促进其转化为新型蛋白质.
结论:
- 识别了与Braak NFT阶段相关的新型受监管的保留内部.
- 提供了翻译circRNAs参与阿尔茨海默病 (AD) 发展的证据.
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