抑制mtDNA转录翻译改变了与阿尔茨海默病相关的生物学
Alexander P Gabrielli1,2, Lesya Novikova1, Amol Ranjan1
1University of Kansas Alzheimer's Disease Research Center, Kansas City, Kansas, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|October 23, 2024
概括
阿尔茨海默病 (AD) 中的线粒体功能障碍触发了细胞反应,并改变了与AD病理相关的基因和蛋白质. 这表明线粒体压力可能会促进AD的发展.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 阿尔茨海默病 (AD) 的特点是线粒体的结构和功能改变.
- 线粒体病理在AD时间线中的确切作用仍在争论中.
研究的目的:
- 调查线粒体功能障碍是否影响涉及AD的基因和蛋白质.
- 探索细胞和分子对被抑制的线粒体翻译的反应.
主要方法:
- 人类神经元细胞 (SH-SY5Y) 和诱导多能干细胞 (iPSC) 衍生的神经元被用氨基醇治疗.
- 氨基醇抑制了线粒体DNA (mtDNA) 编码的转录的翻译.
- 适应性,AD相关基因和AD相关蛋白质反应的特征.
主要成果:
- 抑制线粒体翻译导致mtDNA复制数和细胞中转录的增加.
- 观察到核表达呼吸链mRNA和蛋白质水平的变化.
- 与AD相一致,在粉样蛋白前体蛋白 (APP),β-粉样蛋白 (Aβ),apolipoprotein E (APOE),tau和α-synuclein生物学上注意到了变化.
结论:
- 主要线粒体功能障碍可以诱导补偿性器官反应并改变核基因表达.
- 这些线粒体诱导的变化可能模仿在大脑衰老和AD中观察到的分子现象.
- 线粒体应激可以创造有利于AD病理的环境,这表明它可能是原因或后果.
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