Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System.
Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System.
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神经元限制性沉默因子在中枢神经系统病理生理过程中的作用
DOI：
10.3389/fcell.2022.834620
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发表时间：
2022
影响因子：
5.5
通讯作者：
Zhu C
中科院分区：
文献类型：
--
作者：
Su XJ;Shen BD;Wang K;Song QX;Yang X;Wu DS;Shen HX;Zhu C
神经元限制性沉默因子（NRSF），也称为阻遏元件1（RE-1）沉默转录因子（REST）或X2盒阻遏物（XBR），是一种广泛表达于神经元和非神经元细胞中的锌指转录因子。它是神经系统的主要调节者，NRSF的功能是神经元分化、多样性、可塑性和生存的基础。 NRSF可以与神经元限制性沉默元件（NRSE）结合，招募一些共阻遏物，然后通过表观遗传机制抑制NRSE下游基因的转录。在神经发生中，NRSF不仅充当转录沉默子，介导非神经元细胞中神经元特异性基因的转录抑制，从而赋予神经元细胞特异性，而且还充当转录激活子，诱导神经元分化。许多研究已证实 NRSF 与脑部疾病（例如脑损伤和神经退行性疾病）之间存在关联。过度表达、表达不足或突变可能导致神经系统疾病。在肿瘤发生过程中，NRSF 在神经元肿瘤（如神经母细胞瘤、髓母细胞瘤和嗜铬细胞瘤）中充当癌基因，刺激其增殖，从而导致预后不良。此外，NRSF 介导的选择性靶标基因抑制在神经损伤、癌症和糖尿病引起的神经性疼痛的发生和维持中发挥着重要作用。目前，多种针对NRSF或其共阻遏物的化合物，如REST-VP16和X5050，已被证明在临床上对许多脑部疾病（例如癫痫发作）有效，这意味着NRSF及其共阻遏物可能是神经疾病的潜在且有前途的治疗靶点。在本综述中，我们介绍了NRSF的生物学特性；回顾了迄今为止在理解 NRSF 在神经系统病理生理过程中的作用方面取得的进展，例如神经发生、脑部疾病、神经肿瘤发生和神经性疼痛；并提出了治疗此类脑部疾病的新方法。
The neuron-restrictive silencer factor (NRSF), also known as repressor element 1 (RE-1) silencing transcription factor (REST) or X2 box repressor (XBR), is a zinc finger transcription factor that is widely expressed in neuronal and non-neuronal cells. It is a master regulator of the nervous system, and the function of NRSF is the basis of neuronal differentiation, diversity, plasticity, and survival. NRSF can bind to the neuron-restrictive silencer element (NRSE), recruit some co-repressors, and then inhibit transcription of NRSE downstream genes through epigenetic mechanisms. In neurogenesis, NRSF functions not only as a transcriptional silencer that can mediate the transcriptional inhibition of neuron-specific genes in non-neuronal cells and thus give neuron cells specificity, but also as a transcriptional activator to induce neuronal differentiation. Many studies have confirmed the association between NRSF and brain disorders, such as brain injury and neurodegenerative diseases. Overexpression, underexpression, or mutation may lead to neurological disorders. In tumorigenesis, NRSF functions as an oncogene in neuronal tumors, such as neuroblastomas, medulloblastomas, and pheochromocytomas, stimulating their proliferation, which results in poor prognosis. Additionally, NRSF-mediated selective targets gene repression plays an important role in the development and maintenance of neuropathic pain caused by nerve injury, cancer, and diabetes. At present, several compounds that target NRSF or its co-repressors, such as REST-VP16 and X5050, have been shown to be clinically effective against many brain diseases, such as seizures, implying that NRSF and its co-repressors may be potential and promising therapeutic targets for neural disorders. In the present review, we introduced the biological characteristics of NRSF; reviewed the progress to date in understanding the roles of NRSF in the pathophysiological processes of the nervous system, such as neurogenesis, brain disorders, neural tumorigenesis, and neuropathic pain; and suggested new therapeutic approaches to such brain diseases.
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影响因子：
8
作者：
Das, C. M.;Taylor, P.;Gireud, M.;Singh, A.;Lee, D.;Fuller, G.;Ji, L.;Fangusaro, J.;Rajaram, V.;Goldman, S.;Eberhart, C.;Gopalakrishnan, V.
通讯作者：
Gopalakrishnan, V.
DOI：
10.1016/j.trsl.2014.05.012
发表时间：
2015-01
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Bai G;Ren K;Dubner R
通讯作者：
Dubner R
影响因子：
5.2
作者：
Bergsland, Maria;Covacu, Ruxandra;Brundin, Lou
通讯作者：
Brundin, Lou
影响因子：
4.8
作者：
Ekici, Myriam;Hohl, Mathias;Thiel, Gerald
通讯作者：
Thiel, Gerald
DOI：
10.1073/pnas.0401827101
发表时间：
2004-07-13
影响因子：
11.1
作者：
Bruce, AW;Donaldson, IJ;Buckley, NJ
通讯作者：
Buckley, NJ