Department of Experimental Medicine, University of Genova , 16163 Genova, Italy ; Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia , 16132 Genova, Italy.
Department of Neuroscience, San Raffaele Scientific Institute , 20132 Milano, Italy ; Vita Salute San Raffaele University , 20132 Milano, Italy.
eNeuro. 2015 Jul 10;2(4). doi: 10.1523/ENEURO.0010-15.2015. eCollection 2015 Jul-Aug.
REST [RE1-silencing transcription factor (also called neuron-restrictive silencer factor)] is known to repress thousands of possible target genes, many of which are neuron specific. To date, REST repression has been investigated mostly in stem cells and differentiating neurons. Current evidence demonstrates its importance in adult neurons as well. Low levels of REST, which are acquired during differentiation, govern the expression of specific neuronal phenotypes. REST-dependent genes encode important targets, including transcription factors, transmitter release proteins, voltage-dependent and receptor channels, and signaling proteins. Additional neuronal properties depend on miRNAs expressed reciprocally to REST and on specific splicing factors. In adult neurons, REST levels are not always low. Increases occur during aging in healthy humans. Moreover, extensive evidence demonstrates that prolonged stimulation with various agents induces REST increases, which are associated with the repression of neuron-specific genes with appropriate, intermediate REST binding affinity. Whether neuronal increases in REST are protective or detrimental remains a subject of debate. Examples of CA1 hippocampal neuron protection upon depolarization, and of neurodegeneration upon glutamate treatment and hypoxia have been reported. REST participation in psychiatric and neurological diseases has been shown, especially in Alzheimer's disease and Huntington's disease, as well as epilepsy. Distinct, complex roles of the repressor in these different diseases have emerged. In conclusion, REST is certainly very important in a large number of conditions. We suggest that the conflicting results reported for the role of REST in physiology, pathology, and disease depend on its complex, direct, and indirect actions on many gene targets and on the diverse approaches used during the investigations.
REST（RE1-沉默转录因子（也称为神经元限制沉默因子））已知可抑制数千个可能的靶基因，其中许多是神经元特异性的。迄今为止，REST 抑制作用主要在干细胞和分化神经元中进行了研究。目前的证据表明，它在成年神经元中也很重要。在分化过程中获得的低水平 REST 控制着特定神经元表型的表达。REST 依赖性基因编码重要的靶标，包括转录因子、递质释放蛋白、电压依赖性和受体通道以及信号蛋白。其他神经元特性取决于与 REST 相互表达的 miRNA 和特定的剪接因子。在成年神经元中，REST 水平并不总是低的。在健康人类衰老过程中会增加。此外，大量证据表明，各种试剂的长期刺激会导致 REST 增加，这与具有适当中间 REST 结合亲和力的神经元特异性基因的抑制有关。REST 在神经元中的增加是否具有保护作用还是有害作用仍存在争议。已经报道了 CA1 海马神经元在去极化时的保护作用，以及谷氨酸处理和缺氧时的神经退行性变。REST 参与精神和神经疾病的情况已经得到证实，尤其是在阿尔茨海默病和亨廷顿病以及癫痫中。该抑制剂在这些不同疾病中的独特而复杂的作用已经出现。总之，REST 在许多情况下肯定非常重要。我们认为，REST 在生理学、病理学和疾病中的作用的相互矛盾的结果取决于其对许多基因靶标的复杂、直接和间接作用，以及研究中使用的不同方法。
