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金属诱导的基因毒性事件:在零星和家族ALS之间可能有区别

William Wu Kim^1,2, Gregory Zarus¹, Breanna Alman¹

¹Office of Innovation and Analytics (OIA), Agency for Toxic Substances and Disease Registry(ATSDR), Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS), 4770 Buford Highway, Mailstop S106-5, Chamblee, GA 30341, USA.

|June 25, 2025

概括

接触金属与肌缩性侧面硬化症 (ALS) 有关. 本次审查强调了导致DNA损伤的金属,可能会恶化ALS,并确定了生物标志物和治疗方法的关键数据缺口.

科学领域:

环境毒理学环境毒理学
神经科学是一个神经科学.
遗传学是一个遗传学.

背景情况:

肌缩性侧面硬化症 (ALS) 涉及运动神经元损失,越来越多的证据将DNA损伤与家族 (fALS) 和零星 (sALS) 形式联系起来.
暴露于金属是一种可疑的危险因素,在毒理学概况中观察到基因毒性和神经退行.

研究的目的:

审查ALS病变的金属诱导基因毒性及其在疾病风险中的作用.
总结ALS中DNA损伤生物标志物,并讨论与金属相关的基因毒性机制.
探索fALS和sALS之间的基因毒性生物标志物的潜在区别.

主要方法:

对毒性物质和疾病注册局 (ATSDR) 毒理学概况的全面审查.
对金属暴露,基因毒性和ALS现有文献的分析.
鉴定了15种具有与ALS相关的基因毒性指标的金属.

主要成果:

十五种金属 (例如,,,,) 显示与ALS病变相关的基因毒性.
暴露于金属可以加剧fALS中的遗传突变,并导致sALS中的运动神经元退化.
有证据将重金属暴露与两种ALS形式的基因毒性终点联系在一起,但对于几个标记物存在数据差距.

结论:

暴露于金属与ALS有关,基因毒性影响起着重要作用.
识别尚未探索的基因毒性终点和理解机制对于生物标志物开发和治疗策略至关重要.
对纵向暴露,机制和生物标志物的进一步研究对于ALS的预防和治疗是有必要的.

关键词:

这就是ALS.造成的DNA损伤是DNA损伤.生物标志物生物标志物金属是金属,金属是金属.神经毒性的作用.端粒是什么意思端粒是什么意思

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