A systems approach to prion disease.
A systems approach to prion disease.
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DOI：
10.1038/msb.2009.10
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发表时间：
2009
影响因子：
9.9
通讯作者：
Hood, Leroy E.
中科院分区：
文献类型：
--
作者：
Hwang, Daehee;Lee, Inyoul Y.;Yoo, Hyuntae;Gehlenborg, Nils;Cho, Ji-Hoon;Petritis, Brianne;Baxter, David;Pitstick, Rose;Young, Rebecca;Spicer, Doug;Price, Nathan D.;Hohmann, John G.;DeArmond, Stephen J.;Carlson, George A.;Hood, Leroy E.
朊病毒引起可传播的神经退行性疾病，并通过朊病毒蛋白（PrPC）的正常良性形式构象转换为致病的PrPSc亚型进行复制。疾病的系统方法假定疾病是由相关器官中的生物网络的扰动引起的。我们在疾病进展过程中追踪了八种不同小鼠毒株-朊病毒毒株组合大脑中的整体基因表达，以了解朊病毒毒株、宿主遗传学和PrP浓度对疾病潜伏时间的影响。利用朊病毒生物学和感染的各个方面进行的消减分析确定了333个差异表达基因（DEG）的核心，这些基因似乎是朊病毒疾病的核心。DEG被映射到功能通路和网络，反映定义的神经病理学事件和PrPSc复制和积累，使识别新的模块和模块，可能参与遗传效应的孵育时间和朊病毒株特异性。我们的系统分析提供了一个全面的基础，开发模型的朊病毒复制和疾病，并提出了一些可能的治疗方法。
Prions cause transmissible neurodegenerative diseases and replicate by conformational conversion of normal benign forms of prion protein (PrPC) to disease-causing PrPSc isoforms. A systems approach to disease postulates that disease arises from perturbation of biological networks in the relevant organ. We tracked global gene expression in the brains of eight distinct mouse strain–prion strain combinations throughout the progression of the disease to capture the effects of prion strain, host genetics, and PrP concentration on disease incubation time. Subtractive analyses exploiting various aspects of prion biology and infection identified a core of 333 differentially expressed genes (DEGs) that appeared central to prion disease. DEGs were mapped into functional pathways and networks reflecting defined neuropathological events and PrPSc replication and accumulation, enabling the identification of novel modules and modules that may be involved in genetic effects on incubation time and in prion strain specificity. Our systems analysis provides a comprehensive basis for developing models for prion replication and disease, and suggests some possible therapeutic approaches.
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