Francelle Laetitia, Lotz Caroline, Outeiro Tiago, Brouillet Emmanuel, Merienne Karine
Department of NeuroDegeneration and Restorative Research, University Medical Center Goettingen Goettingen, Germany.
CNRS UMR 7364, Laboratory of Cognitive and Adaptive Neurosciences, University of Strasbourg Strasbourg, France.
Front Hum Neurosci. 2017 Jan 30;11:17. doi: 10.3389/fnhum.2017.00017. eCollection 2017.
Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington's disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the relationship between epigenetic regulations, gene expression and neuronal activity in normal and diseased neurons, including HD neurons. We propose that cell-type specific techniques and 3D-based methods will advance knowledge of epigenome in the context of brain region vulnerability in neurodegenerative diseases. A better understanding of the mechanisms underlying epigenetic changes and of their consequences in neurodegenerative diseases is required to design therapeutic strategies more effective than current strategies based on histone deacetylase (HDAC) inhibitors. Researches in HD may play a driving role in this process.
不平衡的表观遗传调控被认为会促进包括亨廷顿舞蹈症（HD）在内的几种神经退行性疾病的发展，HD是一种被视为表观遗传失调范例的遗传疾病。在这篇综述中，我们试图根据神经表观遗传学的最新进展，探讨有关表观遗传变化在HD中作用的悬而未决的问题。我们特别讨论了使用全基因组规模方法的研究，这些研究为正常和患病神经元（包括HD神经元）中表观遗传调控、基因表达和神经元活动之间的关系提供了见解。我们提出，细胞类型特异性技术和基于三维的方法将推动在神经退行性疾病脑区易损性背景下对表观基因组的认识。为了设计出比目前基于组蛋白去乙酰化酶（HDAC）抑制剂的策略更有效的治疗策略，需要更好地理解表观遗传变化的潜在机制及其在神经退行性疾病中的后果。HD研究可能在这一过程中发挥推动作用。
