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Methylation and acetylation in nervous system development and neurodegenerative disorders.
Ageing Research Reviews ( IF 13.1 ) Pub Date : 2003-05-03 , DOI: 10.1016/s1568-1637(03)00013-8
Mark P Mattson 1
Affiliation  

The cytoarchitecture and cellular signaling mechanisms of the nervous system are complex, and this complexity is reflected at the molecular level with more genes being expressed in the nervous system than in any other tissue. Gene expression and protein function in neural cells can be regulated by methylation and acetylation. Studies of mice deficient in enzymes that control DNA methylation and of animals with a dietary deficiency of folate have established critical roles for methylation in development of the nervous system. Various neuronal proteins including histones and tubulin are regulated by acetylation which appears to serve important functions in the development, stability and plasticity of neuronal networks. Some inherited neurological disorders have recently been linked to mutations in genes that regulate DNA methylation, and alterations in DNA and protein methylation and/or acetylation have been documented in studies of age-related neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Manipulations of methylation and acetylation can affect the vulnerability of neurons to degeneration and apoptosis in experimental models of neurodegenerative disorders, suggesting a contribution to altered methylation and acetylation to the disease processes. Interestingly, dietary factors that influence DNA methylation may affect the risk of neurodegenerative disorders, for example, individuals with low dietary folate intake are at increased risk of Alzheimer's and Parkinson's diseases.

中文翻译:

神经系统发育和神经退行性疾病中的甲基化和乙酰化。

神经系统的细胞结构和细胞信号传导机制很复杂,这种复杂性反映在分子水平上,与其他组织相比,在神经系统中表达的基因更多。神经细胞中的基因表达和蛋白质功能可以通过甲基化和乙酰化来调节。对控制DNA甲基化的酶缺乏的小鼠和饮食中叶酸缺乏的动物的研究已经确定了甲基化在神经系统发育中的关键作用。乙酰化调节包括组蛋白和微管蛋白在内的各种神经元蛋白质,乙酰化似乎在神经元网络的发育,稳定性和可塑性中起重要作用。最近,一些遗传性神经系统疾病与调节DNA甲基化的基因突变有关,年龄相关的神经退行性疾病包括阿尔茨海默氏病(AD),帕金森氏病(PD)和亨廷顿氏病(HD)的研究已证明DNA和蛋白质甲基化和/或乙酰化的改变。在神经退行性疾病的实验模型中,甲基化和乙酰化的操纵可影响神经元对变性和凋亡的脆弱性,表明对疾病过程的甲基化和乙酰化改变的贡献。有趣的是,影响DNA甲基化的饮食因素可能会影响神经退行性疾病的风险,例如,饮食中叶酸摄入量低的人患阿尔茨海默氏病和帕金森氏病的风险增加。
更新日期:2019-11-01
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