Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, Universidad de Zaragoza, IA2, IIS Aragón, 50013 Zaragoza, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto Carlos III, 28029 Madrid, Spain.
Int J Mol Sci. 2022 Oct 20;23(20):12609. doi: 10.3390/ijms232012609.
Prion diseases are transmissible spongiform encephalopathies (TSEs) caused by a conformational conversion of the native cellular prion protein (PrP) to an abnormal, infectious isoform called PrP. Amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's diseases are also known as prion-like diseases because they share common features with prion diseases, including protein misfolding and aggregation, as well as the spread of these misfolded proteins into different brain regions. Increasing evidence proposes the involvement of epigenetic mechanisms, namely DNA methylation, post-translational modifications of histones, and microRNA-mediated post-transcriptional gene regulation in the pathogenesis of prion-like diseases. Little is known about the role of epigenetic modifications in prion diseases, but recent findings also point to a potential regulatory role of epigenetic mechanisms in the pathology of these diseases. This review highlights recent findings on epigenetic modifications in TSEs and prion-like diseases and discusses the potential role of such mechanisms in disease pathology and their use as potential biomarkers.
朊病毒病是由天然细胞朊病毒蛋白（PrP）构象转换为异常、感染性异构体（称为 PrP）引起的传染性海绵状脑病（TSE）。肌萎缩侧索硬化症、阿尔茨海默病、帕金森病和亨廷顿病也被称为朊病毒样疾病，因为它们与朊病毒病具有共同的特征，包括蛋白质错误折叠和聚集，以及这些错误折叠的蛋白质在不同脑区的传播。越来越多的证据表明，表观遗传机制，即 DNA 甲基化、组蛋白的翻译后修饰以及 microRNA 介导的转录后基因调控，参与了朊病毒样疾病的发病机制。关于表观遗传修饰在朊病毒病中的作用知之甚少，但最近的发现也指出了表观遗传机制在这些疾病病理中的潜在调节作用。本综述强调了 TSE 和朊病毒样疾病中表观遗传修饰的最新发现，并讨论了这些机制在疾病病理学中的潜在作用及其作为潜在生物标志物的用途。
