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: 8768667
• 负责人: Min Shi
• 金额: $ 23.18万
• 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 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8768667
• 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; Functional RNA; Future; Gene Chips; Goals; 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; Validation; design; disease diagnosis; disorder control; extracellular; neuroimaging; novel; preference; protein expression; public health relevance; sample collection; scale up; sex; 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，仅在北美就有100多万患者受到折磨，并对社会造成日益沉重的经济负担。迫切需要可靠、准确和廉价的生物标志物，以帮助临床医生进行鉴别诊断，特别是在疾病的早期阶段，或监测疾病进展。使用神经影像学和脑脊液（CSF）蛋白的研究已经显示出希望，但这些潜在的标志物的性能并没有优化，其临床用途是有限的。微小RNA（miRNA）是最近发现的一类小的非编码RNA，可在转录后调节蛋白质水平，在许多细胞过程中发挥重要的调节作用。miRNA表达异常已成为包括PD和其他神经退行性疾病在内的多种疾病的新兴主题。最近的研究还报道了血液、CSF和其他体液中稳定的miRNAs的显著水平，提高了这些miRNAs作为临床有用、可靠和廉价的生物标志物的可能性。在我们的初步研究中，我们已经在从PD患者和健康对照收集的合并的人CSF和血浆样品中检测到超过2，000种miRNA，这些miRNA的一个子集的丰度在PD和对照之间有很大差异。因此，我们假设人体体液中的miRNAs可以作为良好的PD生物标志物。为了验证我们的假设，我们建议使用miRNA阵列进一步分析来自不同阶段的PD患者以及健康和疾病对照的少量合并的人CSF和血浆样本中的miRNA。然后使用定量RT-PCR在个体样本中进一步评价和确认已鉴定的miRNA候选物以及与PD相关的候选物，并考虑CSF和血浆之间或miRNA与同一样本中已知蛋白质标志物水平之间的潜在混杂因素和相关性。该研究为今后利用新的miRNA标记物进行大规模验证和纵向研究奠定了方法学和基础，也可能对理解miRNA在PD发病和发展中的作用做出重要贡献。