MicroRNAs in human body fluids as Parkinson disease biomarkers

人体体液中的 MicroRNA 作为帕金森病的生物标志物

• 批准号: 8862556
• 负责人: Min Shi
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8862556
• 关键词: Age; Alzheimer' s Disease; Biological Assay; Biological Markers; Biological Process; Blood; Body Fluids; Cell physiology; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Clinical; Complex; Dementia; Development; Diagnosis; Differential Diagnosis; Disease; Disease Progression; Economic Burden; Foundations; Future; Gene Chips; Goals; Health; Human; Human body; Impaired cognition; Individual; Lipids; Longitudinal Studies; Measures; Mediating; Membrane; Methodology; Methods; MicroRNAs; Monitor; Motor; Multiple System Atrophy; Neurodegenerative Disorders; North America; Parkinson Disease; Pathogenesis; Patients; Performance; Pharmaceutical Preparations; Pilot Projects; Plasma; Play; Polymerase Chain Reaction; Process; Progressive Supranuclear Palsy; Proteins; RNA; Receiver Operating Characteristics; Regulation; Reporting; Ribonucleases; Role; Sampling; Sensitivity and Specificity; Severity of illness; Small RNA; Societies; Staging; Syndrome; Testing; Time; Treatment outcome; Untranslated RNA; Validation; circulating microRNA; design; disease diagnosis; disorder control; extracellular; neuroimaging; novel; preference; protein expression; sample collection; scale up; sex; targeted treatment; tissue processing; validation studies

DESCRIPTION (provided by applicant): Parkinson disease (PD), one of the most devastating neurodegenerative disorders, afflicts more than one million patients in North America alone and poses an increasing economic burden on society. There is an urgent need for reliable, accurate, and inexpensive biomarkers that can aid clinicians in differential diagnosis, especially during early stages of the disease, or monitoring the disease progression. Studies using neuroimaging and cerebrospinal fluid (CSF) proteins have shown promise, but the performances of these potential markers are not optimized and their clinical utilities are limited. MicroRNAs (miRNAs), a recently discovered class of small, non- coding RNAs that regulate protein levels post-transcriptionally, play important regulatory roles in many cellular processes. Aberrant miRNA expression has become an emerging theme for a wide variety of diseases including PD and other neurodegenerative disorders. Recent studies have also reported significant levels of stable miRNAs in blood, CSF and other body fluids, raising the possibility that these miRNAs could serve as clinically useful, reliable, and inexpensive biomarkers. In our pilot studies, we have detected more than 2,000 miRNAs in pooled human CSF and blood plasma samples collected from patients with PD and healthy controls, with the abundance of a subset of these miRNAs differing substantially between PD and control. We therefore hypothesize that miRNAs in human body fluids may serve as good PD biomarkers. To test our hypothesis, we propose to further profile miRNAs in small-pooled human CSF and plasma samples from patients with PD at different stages and healthy and disease controls, using miRNA arrays. Identified miRNA candidates together with those with established relevance to PD will then be further evaluated and confirmed in individual samples using quantitative RT-PCR, with potential confounding factors and correlations between CSF and plasma or between miRNA and known protein marker levels in the same sample considered. This proposed study will establish methodology and foundation for future large- scale validation and longitudinal studies using novel miRNA markers, and may also contribute significantly to the understanding of the roles of miRNAs in PD pathogenesis and development.

描述（由申请人提供）：帕金森病（PD）是最具破坏性的神经退行性疾病之一，仅在北美就折磨了超过一百万的患者，并给社会带来了日益增加的经济负担。迫切需要可靠，准确且廉价的生物标志物可以帮助临床医生进行鉴别诊断，尤其是在疾病的早期或监测疾病进展的情况下。使用神经影像学和脑脊液（CSF）蛋白质的研究表现出了希望，但是这些潜在标记的性能尚未优化，其临床公用事业也受到限制。 MicroRNA（miRNA）是一种最近发现的小型非编码RNA，在转录后调节蛋白质水平，在许多细胞过程中起着重要的调节作用。异常miRNA表达已成为多种疾病（包括PD和其他神经退行性疾病）的新兴主题。最近的研究还报道了血液，CSF和其他体液中稳定的miRNA水平的显着水平，从而提高了这些miRNA可以作为临床上有用，可靠和廉价的生物标志物的可能性。在我们的试点研究中，我们在PD和健康对照患者中收集的合并的人CSF和血浆样品中检测到了2,000多个miRNA，其中PD和对照之间的这些子集的一部分有很大不同。因此，我们假设人体流体中的miRNA可以用作良好的PD生物标志物。为了检验我们的假设，我们建议使用miRNA阵列在不同阶段和健康和疾病控制的PD患者中进一步介绍来自PD患者的天线人CSF和血浆样品的miRNA。然后，将使用定量RT-PCR在单个样品中进一步评估并确认已鉴定出的miRNA候选物，并在同一样品中使用定量的RT-PCR进行进一步评估和确认，并在单个样品中进行鉴定的MiRNA候选物，以及CSF与血浆之间的潜在混杂因子以及MIRNA与已知蛋白质标记水平之间的相关性。这项提出的研究将建立使用新型miRNA标记的未来大规模验证和纵向研究的方法和基础，也可能有助于理解miRNA在PD发病机理和发育中的作用。