神经退行性变与神经保护领域中新兴的表观遗传学
The emerging field of epigenetics in neurodegeneration and neuroprotection.
作者信息
Hwang Jee-Yeon, Aromolaran Kelly A, Zukin R Suzanne
机构信息
Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center, Room 610, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, New York 10461, USA.
出版信息
Nat Rev Neurosci. 2017 May 18;18(6):347-361. doi: 10.1038/nrn.2017.46.
Abstract
Epigenetic mechanisms - including DNA methylation, histone post-translational modifications and changes in nucleosome positioning - regulate gene expression, cellular differentiation and development in almost all tissues, including the brain. In adulthood, changes in the epigenome are crucial for higher cognitive functions such as learning and memory. Striking new evidence implicates the dysregulation of epigenetic mechanisms in neurodegenerative disorders and diseases. Although these disorders differ in their underlying causes and pathophysiologies, many involve the dysregulation of restrictive element 1-silencing transcription factor (REST), which acts via epigenetic mechanisms to regulate gene expression. Although not somatically heritable, epigenetic modifications in neurons are dynamic and reversible, which makes them good targets for therapeutic intervention.
摘要
表观遗传机制——包括DNA甲基化、组蛋白翻译后修饰以及核小体定位变化——调控几乎所有组织（包括大脑）中的基因表达、细胞分化和发育。在成年期，表观基因组的变化对于学习和记忆等高级认知功能至关重要。惊人的新证据表明表观遗传机制失调与神经退行性疾病有关。尽管这些疾病的潜在病因和病理生理学各不相同，但许多疾病都涉及限制性元件1沉默转录因子（REST）的失调，该因子通过表观遗传机制调节基因表达。尽管神经元中的表观遗传修饰不是体细胞可遗传的，但它们是动态且可逆的，这使其成为治疗干预的良好靶点。
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