Laboratory of Medical Genetics, Department of Translational Research and of New Surgical and Medical Technologies, Medical School, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
Interdepartmental Research Center of Biology and Pathology of Aging, University of Pisa, 56126 Pisa, Italy.
Biomolecules. 2024 Oct 27;14(11):1366. doi: 10.3390/biom14111366.
Individuals affected by neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are dramatically increasing worldwide. Thus, several efforts are being made to develop strategies for stopping or slowing the spread of these illnesses. Although causative genetic variants linked to the onset of these diseases are known, they can explain only a small portion of cases. The etiopathology underlying the neurodegenerative process in most of the patients is likely due to the interplay between predisposing genetic variants and environmental factors. Epigenetic mechanisms, including DNA methylation, are central candidates in translating the effects of environmental factors in genome modulation, and they play a critical role in the etiology of AD, PD, and ALS. Among the main environmental exposures that have been linked to an increased risk for these diseases, accumulating evidence points to the role of heavy metals, pesticides, and air pollutants. These compounds could trigger neurodegeneration through different mechanisms, mainly neuroinflammation and the induction of oxidative stress. However, increasing evidence suggests that they are also capable of inducing epigenetic alterations in neurons. In this article, we review the available literature linking exposure to metals, pesticides, and air pollutants to DNA methylation changes relevant to neurodegeneration.
受神经退行性疾病影响的个体，包括阿尔茨海默病（AD）、帕金森病（PD）和肌萎缩侧索硬化症（ALS），在全球范围内急剧增加。因此，正在努力制定阻止或减缓这些疾病传播的策略。尽管与这些疾病发病相关的致病基因突变已经被确定，但它们只能解释一小部分病例。在大多数患者的神经退行性过程的病因病理学中，可能是由于易感遗传变异和环境因素之间的相互作用。表观遗传机制，包括 DNA 甲基化，是在基因组调节中转导环境因素影响的重要候选者，并且在 AD、PD 和 ALS 的发病机制中发挥着关键作用。在与这些疾病风险增加相关的主要环境暴露中，越来越多的证据表明重金属、农药和空气污染物的作用。这些化合物可能通过主要是神经炎症和氧化应激的诱导，引发神经退行性变。然而，越来越多的证据表明，它们也能够诱导神经元中的表观遗传改变。在本文中，我们回顾了将接触金属、农药和空气污染物与与神经退行性变相关的 DNA 甲基化变化联系起来的现有文献。
