Euroespes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Corunna, Spain.
Int J Mol Sci. 2020 Mar 23;21(6):2220. doi: 10.3390/ijms21062220.
DNA methylation is an epigenetic mechanism by which methyl groups are added to DNA, playing a crucial role in gene expression regulation. The aim of the present study is to compare methylation status of healthy subjects with that of patients with Alzheimer's, Parkinson's or Cerebrovascular diseases. We also analyze methylation status of a transgenic Alzheimer's disease mouse model (3xTg-AD). Our results show that both global methylation ( = 141) and hydroxymethylation ( = 131) levels are reduced in DNA samples from buffy coats of patients with neurodegenerative disorders and age-related cerebrovascular disease. The importance of methylation and hydroxymethylation reduction is stressed by the finding that DNMT3a mRNA levels are also downregulated in buffy coats of patients with Dementia ( = 25). Global methylation is also reduced in brain, liver and serum samples of 3xTg-AD vs. wild type mice, such as DNMT3a mRNA levels that are also decreased in the brain of 3xTg-AD ( = 10). These results suggest that the use of global methylation and hydroxymethylation levels, together with the study of DNMT3a expression, could be useful as a new diagnostic biomarker for these prevalent disorders.
DNA 甲基化是一种表观遗传机制，通过该机制将甲基添加到 DNA 中，在基因表达调控中起着至关重要的作用。本研究的目的是比较健康受试者与阿尔茨海默病、帕金森病或脑血管病患者的甲基化状态。我们还分析了转基因阿尔茨海默病小鼠模型（3xTg-AD）的甲基化状态。我们的研究结果表明，神经退行性疾病和与年龄相关的脑血管病患者的白细胞 DNA 样本中的整体甲基化（ = 141）和羟甲基化（ = 131）水平均降低。DNMT3a mRNA 水平在痴呆症患者的白细胞中也下调（ = 25），这进一步强调了甲基化和羟甲基化减少的重要性。3xTg-AD 与野生型小鼠的大脑、肝脏和血清样本中的整体甲基化水平也降低，3xTg-AD 小鼠的大脑中也降低了 DNMT3a mRNA 水平（ = 10）。这些结果表明，使用整体甲基化和羟甲基化水平，以及研究 DNMT3a 的表达，可能作为这些常见疾病的一种新的诊断生物标志物。
