Key Lab of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China.
Key Lab of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China.
Environ Pollut. 2024 Mar 15;345:123563. doi: 10.1016/j.envpol.2024.123563. Epub 2024 Feb 13.
The pollution of heavy metals (HMs) in the environment is a significant global environmental issue, characterized by its extensive distribution, severe contamination, and profound ecological impacts. Excessive exposure to heavy metal pollutants can damage the nervous system. However, the mechanisms underlying the neurotoxicity of most heavy metals are not completely understood. Epigenetics is defined as a heritable change in gene function that can influence gene and subsequent protein expression levels without altering the DNA sequence. Growing evidence indicates that heavy metals can induce neurotoxic effects by triggering epigenetic changes and disrupting the epigenome. Compared with genetic changes, epigenetic alterations are more easily reversible. Epigenetic reprogramming techniques, drugs, and certain nutrients targeting specific epigenetic mechanisms involved in gene expression regulation are emerging as potential preventive or therapeutic tools for diseases. Therefore, this review provides a comprehensive overview of epigenetic modifications encompassing DNA/RNA methylation, histone modifications, and non-coding RNAs in the nervous system, elucidating their association with various heavy metal exposures. These primarily include manganese (Mn), mercury (Hg), lead (Pb), cobalt (Co), cadmium (Cd), nickel (Ni), sliver (Ag), toxic metalloids arsenic (As), and etc. The potential epigenetic mechanisms in the etiology, precision prevention, and target therapy of various neurodevelopmental disorders or different neurodegenerative diseases are emphasized. In addition, the current gaps in research and future areas of study are discussed. From a perspective on epigenetics, this review offers novel insights for prevention and treatment of neurotoxicity induced by heavy metal pollutants.
重金属（HM）在环境中的污染是一个重大的全球环境问题，其特征为分布广泛、污染严重且对生态环境具有深远影响。过量暴露于重金属污染物会损害神经系统。然而，大多数重金属的神经毒性机制尚未完全阐明。表观遗传学被定义为基因功能的可遗传变化，它可以影响基因及其随后的蛋白质表达水平，而不会改变 DNA 序列。越来越多的证据表明，重金属可以通过触发表观遗传变化和破坏表观基因组来诱导神经毒性效应。与遗传变化相比，表观遗传改变更容易逆转。针对参与基因表达调控的特定表观遗传机制的表观遗传重编程技术、药物和某些营养素正在成为预防或治疗疾病的潜在工具。因此，本综述全面概述了表观遗传修饰，包括神经系统中的 DNA/RNA 甲基化、组蛋白修饰和非编码 RNA，阐明了它们与各种重金属暴露的关联。这些重金属主要包括锰（Mn）、汞（Hg）、铅（Pb）、钴（Co）、镉（Cd）、镍（Ni）、银（Ag）、有毒类金属砷（As）等。强调了各种神经发育障碍或不同神经退行性疾病病因学、精准预防和靶向治疗中的潜在表观遗传机制。此外，还讨论了研究中的当前差距和未来研究领域。从表观遗传学的角度来看，本综述为预防和治疗重金属污染物引起的神经毒性提供了新的见解。
