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核仁应激时神经保护期先于纹状体变性。

A neuroprotective phase precedes striatal degeneration upon nucleolar stress.

机构信息

1] Department of Molecular Biology of the Cell I, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany [2] Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.

出版信息

Cell Death Differ. 2013 Nov;20(11):1455-64. doi: 10.1038/cdd.2013.66. Epub 2013 Jun 14.

DOI:10.1038/cdd.2013.66
PMID:23764776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3792439/
Abstract

The nucleolus is implicated in sensing and responding to cellular stress by stabilizing p53. The pro-apoptotic effect of p53 is associated with several neurodegenerative disorders, including Huntington's disease (HD), which is characterized by the progressive loss of medium spiny neurons (MSNs) in the striatum. Here we show that disruption of nucleolar integrity and function causes nucleolar stress and is an early event in MSNs of R6/2 mice, a transgenic model of HD. Targeted perturbation of nucleolar function in MSNs by conditional knockout of the RNA polymerase I-specific transcription initiation factor IA (TIF-IA) leads to late progressive striatal degeneration, HD-like motor abnormalities and molecular signatures. Significantly, p53 prolongs neuronal survival in TIF-IA-deficient MSNs by transient upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor that inhibits mammalian target of rapamycin signaling and induces autophagy. The results emphasize the initial role of nucleolar stress in neurodegeneration and uncover a p53/PTEN-dependent neuroprotective response.

摘要

核仁参与感知和响应细胞应激，通过稳定 p53 来实现。p53 的促凋亡作用与几种神经退行性疾病有关，包括亨廷顿病（HD），其特征是纹状体中中型棘突神经元（MSNs）的进行性丧失。在这里，我们表明核仁完整性和功能的破坏会导致核仁应激，并且是 R6/2 小鼠（HD 的转基因模型）MSNs 中的早期事件。通过条件敲除 RNA 聚合酶 I 特异性转录起始因子 IA（TIF-IA）靶向破坏 MSNs 中的核仁功能会导致纹状体进行性晚期退化、HD 样运动异常和分子特征。重要的是，p53 通过短暂地上调磷酸酶和张力蛋白同源物缺失的染色体 10（PTEN）来延长 TIF-IA 缺陷型 MSNs 中的神经元存活，PTEN 是一种肿瘤抑制因子，可抑制哺乳动物雷帕霉素靶蛋白信号并诱导自噬。这些结果强调了核仁应激在神经退行性变中的初始作用，并揭示了 p53/PTEN 依赖性神经保护反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/7e79f8be702a/cdd201366f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/894e8bcf92c8/cdd201366f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/727cb32b89af/cdd201366f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/4914846cb524/cdd201366f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/7e79f8be702a/cdd201366f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/894e8bcf92c8/cdd201366f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/7760496847d0/cdd201366f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/166eb12e664d/cdd201366f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/727cb32b89af/cdd201366f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/4914846cb524/cdd201366f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4e/3792439/7e79f8be702a/cdd201366f6.jpg

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2
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Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13428-33. doi: 10.1073/pnas.1204089109. Epub 2012 Jul 30.
3
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4
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8
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