在诱导的认知功能障碍中,N6-甲基氨酸脱甲酶FTO通过YTHDC1-ATF3轴调节神经元的氧化应激
Lixiao Zhou1, Renjie Li1, Fu Wang1
1Department of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing 400016, China.
Journal of hazardous materials
|September 12, 2024
概括
暴露增加了通过FTO改变N6-甲基氨酸 (m6A) 水平的神经元氧化应激. 这项研究确定了一个关键的FTO-ATF3通路和myo-inositol作为一种对神经毒性的保护性代谢物.
科学领域:
- 神经科学是一个神经科学.
- 环境健康 环境健康
- 分子生物学分子生物学
背景情况:
- 环境中的金属,如,与神经系统疾病有关.
- 氧化应激是金属诱导的神经毒性的关键机制,但途径尚不清楚.
- N6-甲基氨酸 (m6A) RNA修饰涉及到细胞过程.
研究的目的:
- 为了研究m6A修饰在诱导的神经元氧化应激中的作用.
- 为了阐明神经毒性中的FTO-ATF3信号轴.
- 为了识别潜在的治疗代谢物对的神经毒性.
主要方法:
- 在体外和体外暴露模型.
- 分析m6A水平和FTO脱甲基酶活性.
- 使用了FTO转基因小鼠和FTO过度表达/淘汰细胞.
- 使用YTHDC1和ATF3.3研究的蛋白质相互作用.
- 进行大脑代谢.
主要成果:
- 暴露增加了m6A水平通过下调FTO.
- 通过ATF3,FTO以m6A依赖的方式调节神经元氧化应激.
- 确定YTHDC1是一个与ATF3.3交互的m6A阅读器.
- 确定了myo-inositol作为一种对诱导的氧化应激和认知功能障碍进行保护的代谢物.
结论:
- 由m6A调节的FTO-ATF3信号轴在由引发的神经元氧化应激中至关重要.
- 米奥伊诺西托尔显示出作为对神经毒性的治疗剂的潜力.
- 这项研究为金属诱导的神经毒性机制和干预措施提供了新的见解.
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