Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
Free Radic Biol Med. 2021 Jul;170:19-33. doi: 10.1016/j.freeradbiomed.2020.12.002. Epub 2020 Dec 8.
One-carbon metabolism provides the methyl groups for both DNA and histone tail methylation reactions, two of the main epigenetic processes that tightly regulate the chromatin structure and gene expression levels. Several enzymes involved in one-carbon metabolism, as well as several epigenetic enzymes, are regulated by intracellular metabolites and redox cofactors, but their expression levels are in turn regulated by epigenetic modifications, in such a way that metabolism and gene expression reciprocally regulate each other to maintain homeostasis and regulate cell growth, survival, differentiation and response to environmental stimuli. Increasing evidence highlights the contribution of impaired one-carbon metabolism and epigenetic modifications in neurodegeneration. This article provides an overview of DNA and histone tail methylation changes in major neurodegenerative disorders, namely Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, discussing the contribution of oxidative stress and impaired one-carbon and redox metabolism to their onset and progression.
一碳代谢为 DNA 和组蛋白尾部甲基化反应提供甲基基团,这是两种主要的表观遗传过程,它们可以紧密调节染色质结构和基因表达水平。一碳代谢中的几种酶以及几种表观遗传酶受到细胞内代谢物和氧化还原辅助因子的调节,但它们的表达水平又受到表观遗传修饰的调节,因此代谢和基因表达相互调节以维持内稳态并调节细胞生长、存活、分化和对环境刺激的反应。越来越多的证据强调了受损的一碳代谢和表观遗传修饰在神经退行性变中的作用。本文概述了主要神经退行性疾病(即阿尔茨海默病、帕金森病和肌萎缩侧索硬化症)中 DNA 和组蛋白尾部甲基化的变化,讨论了氧化应激以及一碳和氧化还原代谢受损对其发病和进展的影响。