外源性气态甲醛 (FA) 因其化学反应活性和已证实的致突变和致癌特性，特别是其破坏 DNA 和影响人类健康的能力而被认为是一种重要的室内空气污染物。尽管人们越来越关注外源性FA对人类健康的不利影响，但目前的研究在很大程度上忽视了内源性FA对大脑的潜在不利影响。据观察，由于参与 FA 代谢的酶的表达和活性失调，内源性 FA 会在衰老的大脑中积聚。令人惊讶的是，过量的 FA 与阿尔茨海默病 (AD)、帕金森病 (PD) 和脑癌等神经退行性疾病的发生有关。值得注意的是，FA 不仅能够引发 DNA 双链断裂，还能诱导 DNA-DNA、DNA-RNA 和 DNA-蛋白质交联的形成，从而进一步加剧这些脑部疾病的进展。然而，最近的研究发现，FA 抗性基因核酸外切酶-1 (EXO1) 和 FA 清除剂有可能减轻 FA 毒性，为减轻或修复 FA 诱导的 DNA 损伤提供了一种有前景的策略。本综述对 FA 代谢对大脑衰老的影响以及 FA 损伤的 DNA 对神经系统疾病进展的影响提供了新颖的见解。© 2024。作者。

Exogenous gaseous formaldehyde (FA) is recognized as a significant indoor air pollutant due to its chemical reactivity and documented mutagenic and carcinogenic properties, particularly in its capacity to damage DNA and impact human health. Despite increasing attention on the adverse effects of exogenous FA on human health, the potential detrimental effects of endogenous FA in the brain have been largely neglected in current research. Endogenous FA have been observed to accumulate in the aging brain due to dysregulation in the expression and activity of enzymes involved in FA metabolism. Surprisingly, excessive FA have been implicated in the development of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and brain cancers. Notably, FA has the ability to not only initiate DNA double strand breaks but also induce the formation of crosslinks of DNA-DNA, DNA-RNA, and DNA-protein, which further exacerbate the progression of these brain diseases. However, recent research has identified that FA-resistant gene exonuclease-1 (EXO1) and FA scavengers can potentially mitigate FA toxicity, offering a promising strategy for mitigating or repairing FA-induced DNA damage. The present review offers novel insights into the impact of FA metabolism on brain ageing and the contribution of FA-damaged DNA to the progression of neurological disorders.© 2024. The Author(s).