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早年接触铅 (Pb) 和 DNA 甲基化的变化:与阿尔茨海默病的相关性。

Early life exposure to lead (Pb) and changes in DNA methylation: relevance to Alzheimer's disease.

机构信息

George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Avedisian Hall, Lab: 390, 7 Greenhouse Road, Kingston, RI 02881, USA.

出版信息

Rev Environ Health. 2019 Jun 26;34(2):187-195. doi: 10.1515/reveh-2018-0076.

Abstract

Recent advances in neuroepigenetics have revealed its essential role in governing body function and disease. Epigenetics regulates an array of mechanisms that are susceptible to undergoing alteration by intracellular or extracellular factors. DNA methylation, one of the most extensively studied epigenetic markers is involved in the regulation of gene expression and also plays a vital role in neuronal development. The epigenome is most vulnerable during early the embryonic stage and perturbation in DNA methylation during this period can result in a latent outcome which can persist during the entire lifespan. Accumulating evidence suggests that environmental insults during the developmental phase can impart changes in the DNA methylation landscape. Based on reports on human subjects and animal models this review will explore the evidence on how developmental exposure of the known environmental pollutant, lead (Pb), can induce changes in the DNA methylation of genes which later can induce development of neurodegenerative disorders like Alzheimer's disease (AD).

摘要

神经表观遗传学的最新进展揭示了其在调节身体功能和疾病方面的重要作用。表观遗传学调节着一系列易受细胞内或细胞外因素改变的机制。DNA 甲基化是研究最广泛的表观遗传标记之一,参与基因表达的调控,在神经元发育中也起着至关重要的作用。表观基因组在胚胎早期最为脆弱,在此期间 DNA 甲基化的干扰可能导致潜伏的后果,这种后果可能会持续整个生命周期。越来越多的证据表明,发育阶段的环境损伤会导致 DNA 甲基化图谱发生变化。基于对人类和动物模型的报告,本综述将探讨已知环境污染物铅(Pb)在发育阶段暴露如何诱导基因 DNA 甲基化的变化,而这些变化后来可能会导致阿尔茨海默病(AD)等神经退行性疾病的发生。

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