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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.

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。

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