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三种神经退行性疾病(散发性克雅氏病(sCJD)、致死性家族性失眠症(FFI)和阿尔茨海默病(AD))皮质区域全球基因表达谱的异同分析。

Analyses of the similarity and difference of global gene expression profiles in cortex regions of three neurodegenerative diseases: sporadic Creutzfeldt-Jakob disease (sCJD), fatal familial insomnia (FFI), and Alzheimer's disease (AD).

作者信息

Tian Chan, Liu Di, Xiang Wei, Kretzschmar Hans A, Sun Qing-Lan, Gao Chen, Xu Yin, Wang Hui, Fan Xue-Yu, Meng Ge, Li Wei, Dong Xiao-Ping

机构信息

State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changbai Rd 155, Beijing, 102206, People's Republic of China.

出版信息

Mol Neurobiol. 2014 Oct;50(2):473-81. doi: 10.1007/s12035-014-8758-x. Epub 2014 Jun 7.

Abstract

Neurodegenerative disease is a general designation for the disorders that are progressive loss of structure or function and final death of neurons, including Alzheimer's, Parkinson's, Huntington's, prion diseases, etc. In this study, we comparatively analyzed 21 individual microarray data sets of the cortex tissues from 11 sporadic Creutzfeldt-Jakob disease (sCJD), 3 fatal familial insomnia (FFI), 3 Alzheimer's disease (AD), and 4 normal controls. After normalization, a collection of 730 differently expressed sets (DESets) were obtained by comparison of the data of three diseases with their original controls. Principal component analysis (PCA) showed a background-related distribution within the groups of FFI, AD, and normal control, but two apparently different subgroups within the group of sCJD were observed. Review of the clinical materials of 11 sCJD patients identified the difference in brain PrP(Sc) deposits between two subgroups. Hierarchical cluster analysis illustrated the relatively independent clusters of normal controls, FFIs, six sCJD cases (subgroup 1) with more PrP(Sc) deposits, respectively, while an overlapped cluster of five cases of sCJD2 (subgroup 2) with less PrP(Sc) deposits and AD patients. Despite of the presence of special gene expressions, many common features were found among those neurodegenerative diseases. The most commonly changed biological processes (BPs) were signal transduction, synaptic transmission, and neuropeptide signaling pathway. The most commonly changed pathways were MAPK signaling pathway, Parkinson's disease, and oxidative phosphorylation. Our data here provide the similarity and difference in global gene expressions among the patients with sCJD, FFI, and AD, which may help to understand the common mechanism of neurodegenerative diseases.

摘要

神经退行性疾病是指结构或功能逐渐丧失以及神经元最终死亡的一类疾病的统称,包括阿尔茨海默病、帕金森病、亨廷顿病、朊病毒病等。在本研究中,我们对来自11例散发性克雅氏病(sCJD)、3例致死性家族性失眠症(FFI)、3例阿尔茨海默病(AD)和4例正常对照的皮质组织的21个个体微阵列数据集进行了比较分析。标准化后,通过将三种疾病的数据与其原始对照进行比较,获得了730个差异表达集(DESets)。主成分分析(PCA)显示FFI、AD和正常对照组内存在与背景相关的分布,但在sCJD组中观察到两个明显不同的亚组。回顾11例sCJD患者的临床资料,发现两个亚组之间脑PrP(Sc)沉积存在差异。层次聚类分析表明,正常对照组、FFI组、6例PrP(Sc)沉积较多的sCJD病例(亚组1)分别形成相对独立的聚类,而5例PrP(Sc)沉积较少的sCJD病例(亚组2)和AD患者形成一个重叠聚类。尽管存在特殊的基因表达,但在这些神经退行性疾病中发现了许多共同特征。最常发生变化的生物学过程(BPs)是信号转导、突触传递和神经肽信号通路。最常发生变化的通路是丝裂原活化蛋白激酶(MAPK)信号通路、帕金森病和氧化磷酸化。我们的数据揭示了sCJD、FFI和AD患者在整体基因表达上的异同,这可能有助于理解神经退行性疾病的共同机制。

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