• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biomarker Research >Whole gene expression profile in blood reveals multiple pathways deregulation in R6/2 mouse model
【24h】

Whole gene expression profile in blood reveals multiple pathways deregulation in R6/2 mouse model

机译：血液中的全基因表达谱揭示了R6 / 2小鼠模型中的多种途径失控

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

BackgroundHuntington Disease (HD) is a progressive neurological disorder, with pathological manifestations in brain areas and in periphery caused by the ubiquitous expression of mutant Huntingtin protein. Transcriptional dysregulation is considered a key molecular mechanism responsible of HD pathogenesis but, although numerous studies investigated mRNA alterations in HD, so far none evaluated a whole gene expression profile in blood of R6/2 mouse model. FindingsTo discover novel pathogenic mechanisms and potential peripheral biomarkers useful to monitor disease progression or drug efficacy, a microarray study was performed in blood of R6/2 at manifest stage and wild type littermate mice. This approach allowed to propose new peripheral molecular processes involved in HD and to suggest different panels of candidate biomarkers. Among the discovered deregulated processes, we focused on specific ones: complement and coagulation cascades, PPAR signaling, cardiac muscle contraction, and dilated cardiomyopathy pathways. Selected genes derived from these pathways were additionally investigated in other accessible tissues to validate these matrices as source of biomarkers, and in brain, to link central and peripheral disease manifestations. ConclusionsOur findings validated the skeletal muscle as suitable source to investigate peripheral transcriptional alterations in HD and supported the hypothesis that immunological alteration may contribute to neurological degeneration. Moreover, the identification of altered signaling in mouse blood enforce R6/2 transgenic mouse as a powerful HD model while suggesting novel disease biomarkers for pre-clinical investigation.
机译：背景亨廷顿病（HD）是一种进行性神经系统疾病，在大脑区域和周围都有病理性表现，这是由突变的Huntingtin蛋白的普遍表达引起的。转录失调被认为是导致HD发病的关键分子机制，但是，尽管许多研究调查了HD中的mRNA改变，但到目前为止，没有人评估R6 / 2小鼠模型血液中的完整基因表达谱。为了发现可用于监测疾病进展或药物疗效的新的致病机制和潜在的外周生物标志物，在明显阶段的R6 / 2和野生型同窝小鼠的血液中进行了微阵列研究。这种方法可以提出涉及HD的新的外周分子过程，并可以提出不同的候选生物标志物组。在发现的失控过程中，我们专注于特定过程：补体和凝血级联，PPAR信号传导，心肌收缩和扩张型心肌病通路。此外，还在其他可及组织中研究了从这些途径中选出的基因，以验证这些基质是否是生物标志物的来源，并在大脑中将中枢和外周疾病表现联系起来。结论我们的发现证实骨骼肌是研究HD外周转录改变的合适来源，并支持免疫改变可能导致神经退行性变的假说。此外，小鼠血液中信号传导改变的鉴定将R6 / 2转基因小鼠作为一种强大的HD模型，同时为临床前研究提出了新的疾病生物标记。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号