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神经干细胞和定向分化神经元前体细胞功能调控的细胞内信号转导的特定特征。

Specific Features of Intracellular Signal Transduction in the Regulation of Functions of Neural Stem Cells and Committed Neuronal Progenitors.

机构信息

E. D. Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.

出版信息

Bull Exp Biol Med. 2021 Feb;170(4):522-527. doi: 10.1007/s10517-021-05100-y. Epub 2021 Mar 16.

Abstract

We studied the role of NF-κB-, cAMP/PKA-, JAKs/STAT3-, ERK1/2-, p38-, JNK- and p53- mediated signaling pathways in the realization of the growth potential of neural stem cells and committed neuronal progenitors under in vitro conditions. The method of pharmacological blockade with selective inhibitors of individual signaling molecules revealed some principal differences in their role in the determination of the proliferation and differentiation status of progenitor cells of different classes. Analysis of the peculiarities of intracellular signaling in cells and comparison of the role of its individual elements attest to the prospects of developing new drugs with neuroregenerative activity based on STAT3 inhibitors or JNK activators. These modulations of activity of signaling molecules can stimulate the realization of the growth potential of committed neuronal progenitors and neutral stem cells, respectively. The blockade of STAT3 and an increase in the content of phosphorylated forms of JNK had no "negative" effects on the functioning of multipotent neural stem cells and committed neuronal progenitors, respectively.

摘要

我们研究了 NF-κB、cAMP/PKA、JAKs/STAT3、ERK1/2、p38、JNK 和 p53 介导的信号通路在体外条件下神经干细胞和定向神经元祖细胞实现生长潜能中的作用。用选择性信号分子抑制剂进行药理学阻断的方法揭示了它们在决定不同类别的祖细胞增殖和分化状态中的作用的一些主要差异。对细胞内信号转导的特点进行分析,并比较其各个元素的作用,证明了基于 STAT3 抑制剂或 JNK 激活剂开发具有神经再生活性的新药的前景。这些信号分子活性的调节可以分别刺激定向神经元祖细胞和神经干祖细胞生长潜能的实现。STAT3 的阻断和 JNK 磷酸化形式含量的增加分别对多能神经干细胞和定向神经元祖细胞的功能没有“负面”影响。

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