Zimmer-Bensch Geraldine
Division of Functional Epigenetics in the Animal Model, Institute for Biology II, RWTH Aachen University, Worringerweg 3, 52074 Aachen, Germany.
Epigenomes. 2020 Jul 31;4(3):15. doi: 10.3390/epigenomes4030015.
In light of our aging population, neurodegenerative disorders are becoming a tremendous challenge, that modern societies have to face. They represent incurable, progressive conditions with diverse and complex pathological features, followed by catastrophic occurrences of massive neuronal loss at the later stages of the diseases. Some of these disorders, like Huntington's disease (HD), rely on defined genetic factors. HD, as an incurable, fatal hereditary neurodegenerative disorder characterized by its mid-life onset, is caused by the expansion of CAG trinucleotide repeats coding for glutamine (Q) in exon 1 of the huntingtin gene. Apart from the genetic defect, environmental factors are thought to influence the risk, onset and progression of HD. As epigenetic mechanisms are known to readily respond to environmental stimuli, they are proposed to play a key role in HD pathogenesis. Indeed, dynamic epigenomic remodeling is observed in HD patients and in brains of HD animal models. Epigenetic signatures, such as DNA methylation, histone variants and modifications, are known to influence gene expression and to orchestrate various aspects of neuronal physiology. Hence, deciphering their implication in HD pathogenesis might open up new paths for novel therapeutic concepts, which are discussed in this review.
鉴于我们的人口老龄化，神经退行性疾病正成为现代社会不得不面对的巨大挑战。它们代表着无法治愈的、进行性的病症，具有多样且复杂的病理特征，在疾病后期会出现大量神经元灾难性损失。其中一些疾病，如亨廷顿舞蹈病（HD），依赖于特定的遗传因素。HD是一种无法治愈的、致命的遗传性神经退行性疾病，其特征为中年发病，由亨廷顿基因外显子1中编码谷氨酰胺（Q）的CAG三核苷酸重复序列扩增所致。除了遗传缺陷外，环境因素也被认为会影响HD的风险、发病和进展。由于已知表观遗传机制容易对环境刺激做出反应，因此有人提出它们在HD发病机制中起关键作用。事实上，在HD患者和HD动物模型的大脑中都观察到了动态的表观基因组重塑。表观遗传特征，如DNA甲基化、组蛋白变体和修饰，已知会影响基因表达并协调神经元生理的各个方面。因此，解读它们在HD发病机制中的作用可能会为新的治疗理念开辟新途径，本文将对此进行讨论。
