Van den Hove Daniel L, Kompotis Konstantinos, Lardenoije Roy, Kenis Gunter, Mill Jonathan, Steinbusch Harry W, Lesch Klaus-Peter, Fitzsimons Carlos P, De Strooper Bart, Rutten Bart P F
School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine, and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, the Netherlands; Division of Molecular Psychiatry, Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Würzburg, Würzburg, Germany.
School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine, and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, the Netherlands.
Neurobiol Aging. 2014 Apr;35(4):731-45. doi: 10.1016/j.neurobiolaging.2013.10.082. Epub 2013 Oct 18.
Alzheimer's disease (AD) is a complex neurodegenerative disorder involving dysregulation of many biological pathways at multiple levels. Classical epigenetic mechanisms, including DNA methylation and histone modifications, and regulation by microRNAs (miRNAs), are among the major regulatory elements that control these pathways at the molecular level, with epigenetic modifications regulating gene expression transcriptionally and miRNAs suppressing gene expression posttranscriptionally. Epigenetic mechanisms and miRNAs have recently been shown to closely interact with each other, thereby creating reciprocal regulatory circuits, which appear to be disrupted in neuronal and glial cells affected by AD. Here, we review those miRNAs implicated in AD that are regulated by promoter DNA methylation and/or chromatin modifications and, which frequently direct the expression of constituents of the epigenetic machinery, concluding with the delineation of a complex epigenetic-miRNA regulatory network and its alterations in AD.
阿尔茨海默病（AD）是一种复杂的神经退行性疾病，涉及多个层面上许多生物途径的失调。经典的表观遗传机制，包括DNA甲基化和组蛋白修饰，以及微小RNA（miRNA）的调控，是在分子水平上控制这些途径的主要调控元件，表观遗传修饰在转录水平上调节基因表达，而miRNA在转录后水平上抑制基因表达。最近的研究表明，表观遗传机制和miRNA相互之间密切作用，从而形成相互调控回路，而在受AD影响的神经元和神经胶质细胞中，这些调控回路似乎被破坏。在此，我们综述了那些受启动子DNA甲基化和/或染色质修饰调控、且经常指导表观遗传机制成分表达的与AD相关的miRNA，并勾勒出一个复杂的表观遗传-miRNA调控网络及其在AD中的改变。
