关于颗粒物和阿尔茨海默病的新视角:从不良结果路径框架的洞察力
Shuang-Jian Qin1, Qing-Guo Zeng1, Hui-Xian Zeng1
1Joint International Research Laboratory of Environment and Health, Ministry of Education, Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.
Environmental pollution (Barking, Essex : 1987)
|January 5, 2025
概括
颗粒物暴露与阿尔茨海默氏病 (AD) 有关. 本研究使用不利结果途径 (AOP) 框架详细介绍了将PM暴露与AD发展联系起来的分子机制,识别了关键基因和细胞事件.
科学领域:
- 环境健康 环境健康
- 神经科学是一个神经科学.
- 毒理学 毒理学 毒理学
背景情况:
- 阿尔茨海默病 (AD) 是导致痴呆的主要原因,占病例的50-75%.
- 有证据表明,暴露于颗粒物 (PM) 和AD之间存在联系,但潜在的机制需要进一步阐明.
- 现有研究在了解将PM暴露与AD病原发生联系起来的确切途径方面存在相当大的差距.
研究的目的:
- 为了澄清将颗粒物 (PM) 暴露与阿尔茨海默氏病 (AD) 暴露在多个生物层面之间的机制.
- 构建和验证一个不利结果路径 (AOP) 网络,详细说明PM-AD关系.
- 确定关键的基因和表型,涉及从PM暴露到AD的途径.
主要方法:
- 一个基于化学现象型相互作用网络的工作流被用来整合来自公共数据库 (CTD,DisGeNET,MalaCards,GO,KEGG) 的数据.
- 基因和表型被确定为分子启动事件 (MIE) 和关键事件 (KE),以建立一个预测性PM-Gene-Phenotype-AD AOP网络.
- 使用经合组织指导方针评估了不良结果途径 (AOP) 网络,以验证PM对AD的影响.
主要成果:
- 该研究产生了一个经过验证的AOP网络,详细说明了从PM暴露到AD的途径.
- 据证明,暴露于颗粒物 (PM) 会增加粉样蛋白前体蛋白 (APP) 和GSK3B的表达.
- 暴露于PM会导致亡的增加,认知和记忆的受损,最终导致阿尔茨海默病 (AD).
结论:
- 这是首个专门设计用于阐明在阿尔茨海默氏症 (AD) 中暴露于PM的机制的不良结果途径 (AOP) 框架.
- 基于网络的方法成功地弥合了理解PM-AD连接的机制差距.
- 该方法为构建其他环境暴露和疾病的AOP框架提供了基础.
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