Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center, Room 610, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY 10461, USA.
Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center, Room 610, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY 10461, USA.
Curr Opin Neurobiol. 2018 Feb;48:193-200. doi: 10.1016/j.conb.2017.12.008. Epub 2018 Jan 30.
The restrictive element-1 silencing transcription factor)/NRSF (neuron-restrictive silencing factor (NRSF) is a transcriptional repressor which acts via epigenetic remodeling to silence target genes. Emerging evidence indicates that REST is a master transcriptional regulator of neuron-specific genes not only in neurogenesis and neuronal differentiation, but also in differentiated neurons during the critical period in postnatal brain development, where it plays a role in fine-tuning of genes involved in synaptic plasticity, and in normal aging, where it promotes neuroprotection by repressing genes involved in oxidative stress and β-amyloid toxicity. This review focuses on recent findings that dysregulation of REST and REST-dependent epigenetic remodeling provide a central mechanism critical to the progressive neurodegeneration associated with neurologic disorders and diseases including global ischemia, stroke, epilepsy, Alzheimer's and Huntington's disease.
阻遏元件-1 沉默转录因子（REST）/NRSF（神经元限制沉默因子（NRSF））是一种转录阻遏物，通过表观遗传重塑来沉默靶基因。新出现的证据表明，REST 是神经元特异性基因的主要转录调节剂，不仅在神经发生和神经元分化中，而且在出生后大脑发育的关键时期的分化神经元中，它在参与突触可塑性的基因的微调中发挥作用，在正常衰老中，它通过抑制参与氧化应激和β-淀粉样毒性的基因来促进神经保护。这篇综述重点介绍了最近的发现，即 REST 的失调和 REST 依赖性表观遗传重塑提供了一个关键机制，对与神经障碍和疾病相关的进行性神经退行性变至关重要，包括全身缺血、中风、癫痫、阿尔茨海默病和亨廷顿病。
