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本文引用的文献

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AAV.shRNA-mediated downregulation of ROCK2 attenuates degeneration of dopaminergic neurons in toxin-induced models of Parkinson's disease in vitro and in vivo.AAV.shRNA 介导的 ROCK2 下调可减轻体内外毒素诱导的帕金森病模型中多巴胺能神经元的变性。
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ARF: a versatile DNA damage response ally at the crossroads of development and tumorigenesis.ARF:一个多功能的 DNA 损伤反应伙伴,位于发育和肿瘤发生的十字路口。
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AKT regulates NPM dependent ARF localization and p53mut stability in tumors.AKT在肿瘤中调节NPM依赖的ARF定位和p53mut稳定性。
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Granulocyte colony-stimulating factor improves neuron survival in experimental spinal cord injury by regulating nucleophosmin-1 expression.粒细胞集落刺激因子通过调节核磷蛋白-1的表达来提高实验性脊髓损伤中神经元的存活率。
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Pharmacologic inhibition of ROCK2 suppresses amyloid-β production in an Alzheimer's disease mouse model.药物抑制 ROCK2 可减少阿尔茨海默病小鼠模型中的淀粉样 β 生成。
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Nucleolar dysfunction in Huntington's disease.亨廷顿舞蹈病中的核仁功能障碍。
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In vivo modulation of polo-like kinases supports a key role for PLK2 in Ser129 α-synuclein phosphorylation in mouse brain.体内调节 Polo 样激酶支持 PLK2 在小鼠脑内 Ser129α-突触核蛋白磷酸化中的关键作用。
Neuroscience. 2014 Jan 3;256:72-82. doi: 10.1016/j.neuroscience.2013.09.061. Epub 2013 Oct 12.
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Role of cysteine 288 in nucleophosmin cytoplasmic mutations: sensitization to toxicity induced by arsenic trioxide and bortezomib.半胱氨酸 288 在核仁磷酸蛋白细胞质突变中的作用:砷剂三氧化二砷和硼替佐米诱导的毒性敏感性。
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A neuroprotective phase precedes striatal degeneration upon nucleolar stress.核仁应激时神经保护期先于纹状体变性。
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SOD2 in mitochondrial dysfunction and neurodegeneration.SOD2 在线粒体功能障碍和神经退行性变中的作用。
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对核磷蛋白/B23调节神经元活力的见解。

Insights into the regulation of neuronal viability by nucleophosmin/B23.

作者信息

Pfister Jason A, D'Mello Santosh R

机构信息

Department of Biological Sciences, University of Texas at Dallas, Richardson, TX 75080, USA Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA.

Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA

出版信息

Exp Biol Med (Maywood). 2015 Jun;240(6):774-86. doi: 10.1177/1535370215579168. Epub 2015 Apr 22.

DOI:10.1177/1535370215579168
PMID:25908633
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4640450/
Abstract

The vastness of the neuronal network that constitutes the human brain proves challenging when trying to understand its complexity. Furthermore, due to the senescent state they enter into upon maturation, neurons lack the ability to regenerate in the face of insult, injury or death. Consequently, their excessive death can be detrimental to the proper functioning of the brain. Therefore, elucidating the mechanisms regulating neuronal survival is, while challenging, of great importance as the incidence of neurological disease is becoming more prevalent in today's society. Nucleophosmin/B23 (NPM) is an abundant and ubiquitously expressed protein that regulates vital cellular processes such as ribosome biogenesis, cell proliferation and genomic stability. As a result, it is necessary for proper embryonic development, but has also been implicated in many cancers. While highly studied in the context of proliferative cells, there is a lack of understanding NPM's role in post-mitotic neurons. By exploring its role in healthy neurons as well as its function in the regulation of cell death and neurodegeneration, there can be a better understanding of how these diseases initiate and progress. Owing to what is thus far known about its function in the cell, NPM could be an attractive therapeutic target in the treatment of neurodegenerative diseases.

摘要

当试图理解构成人类大脑的神经网络的复杂性时,其广阔性被证明是具有挑战性的。此外,由于神经元在成熟后进入衰老状态,它们在面对损伤、伤害或死亡时缺乏再生能力。因此,它们的过度死亡可能对大脑的正常功能有害。所以,阐明调节神经元存活的机制虽然具有挑战性,但由于神经疾病的发病率在当今社会越来越普遍,这一点非常重要。核仁磷酸蛋白/B23(NPM)是一种大量且广泛表达的蛋白质,它调节诸如核糖体生物合成、细胞增殖和基因组稳定性等重要的细胞过程。因此,它对正常的胚胎发育是必需的,但也与许多癌症有关。虽然在增殖细胞的背景下对其进行了深入研究,但人们对NPM在有丝分裂后神经元中的作用缺乏了解。通过探索其在健康神经元中的作用以及其在细胞死亡和神经退行性变调节中的功能,可以更好地理解这些疾病是如何发生和发展的。鉴于目前已知其在细胞中的功能,NPM可能是治疗神经退行性疾病的一个有吸引力的治疗靶点。