它调节的种子:自然反感转录作为神经退行性疾病中单基因控制开关
Debomoy K Lahiri1, Bryan Maloney2, Ruizhi Wang3
1Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
自然反感转录 (NAT) 调节基因表达和蛋白质水平,影响神经退行性疾病,如阿尔茨海默氏症和帕金森氏症. 了解NAT为这些疾病提供了潜在的新治疗点.
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
- 遗传学 是一个遗传学.
背景情况:
- 神经退行性疾病,如阿尔茨海默氏症 (AD),帕金森氏症 (PD) 和前性痴呆症 (FTD) 与特定蛋白质失调有关.
- 基因表达受到转录因子,microRNA和自然反意义转录 (NAT) 的严格控制.
- NATs是非编码RNAs,在调节mRNA水平,拼接和关键基因的翻译中发挥重要作用,这些基因参与神经退行.
研究的目的:
- 探索NATs在调节神经退行性疾病相关蛋白质表达中的作用.
- 研究如何在致病性条件下对NAT进行上调或下调.
- 确定NAT作为预防或治疗与年龄有关的神经系统疾病的潜在治疗点.
主要方法:
- 对NATs对基因表达的调控机制的分析,包括mRNA翻译和DNA (去甲基化).
- 检查NAT结构,包括内子和外子,以及它们与基因,前mRNA和成熟RNA的结合相互作用.
- 具体NAT的案例研究,如MAPT-AS1 (降低调节tau) 和BACE1-AS (升高调节β-粉样蛋白前体蛋白),在疾病发病的背景下.
主要成果:
- NATs可以降低调节 (例如,MAPT-AS1) 或提高调节 (例如,BACE1-AS) 关键蛋白质的翻译,这些蛋白质与神经退行性疾病有关.
- 某些NATs的表达与疾病进展并行,在疾病条件下",致病性"NATs增加和"保护性"NATs减少.
- NATs表现出超出mRNA翻译的多种调节功能,影响DNA甲基化和其他基因表达步骤.
结论:
- NATs代表了内源性基因调节的重要但未被充分探索的层.
- NATs的失调与神经退行性疾病的发病密切相关.
- 向NAT为神经退行性疾病和与衰老有关的疾病提供了一个有前途的新疗法策略.
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