Schwienbacher Christine, Foco Luisa, Picard Anne, Corradi Eloina, Serafin Alice, Panzer Jörg, Zanigni Stefano, Blankenburg Hagen, Facheris Maurizio F, Giannini Giulia, Falla Marika, Cortelli Pietro, Pramstaller Peter P, Hicks Andrew A
Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, 39100, Bolzano, Italy.
Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum-University of Bologna, 40126, Bologna, Italy.
J Mol Neurosci. 2017 Jun;62(2):244-254. doi: 10.1007/s12031-017-0926-9. Epub 2017 May 24.
Parkinson's disease (PD) diagnosis is based on the assessment of motor symptoms, which manifest when more than 50% of dopaminergic neurons are degenerated. To date, no validated biomarkers are available for the diagnosis of PD. The aims of the present study are to evaluate whether plasma and white blood cells (WBCs) are interchangeable biomarker sources and to identify circulating plasma-based microRNA (miRNA) biomarkers for an early detection of PD. We profiled plasma miRNA levels in 99 L-dopa-treated PD patients from two independent data collections, in ten drug-naïve PD patients, and in unaffected controls matched by sex and age. We evaluated expression levels by reverse transcription and quantitative real-time PCR (RT-qPCR) and combined the results from treated PD patients using a fixed effect inverse-variance weighted meta-analysis. We revealed different expression profiles comparing plasma and WBCs and drug-naïve and L-dopa-treated PD patients. We observed an upregulation trend for miR-30a-5p in L-dopa-treated PD patients and investigated candidate target genes by integrated in silico analyses. We could not analyse miR-29b-3p, normally expressed in WBCs, due to the very low expression in plasma. We observed different expression profiles in WBCs and plasma, suggesting that they are both suitable but not interchangeable peripheral sources for biomarkers. We revealed miR-30a-5p as a potential biomarker for PD in plasma. In silico analyses suggest that miR-30a-5p might have a regulatory role in mitochondrial dynamics and autophagy. Further investigations are needed to confirm miR-30a-5p deregulation and targets and to investigate the influence of L-dopa treatment on miRNA expression levels.
帕金森病(PD)的诊断基于运动症状评估,当超过50%的多巴胺能神经元发生退化时这些症状才会显现。迄今为止,尚无经过验证的生物标志物可用于PD的诊断。本研究的目的是评估血浆和白细胞(WBC)是否为可互换的生物标志物来源,并识别基于循环血浆的微小RNA(miRNA)生物标志物以早期检测PD。我们在来自两个独立数据收集的99例接受左旋多巴治疗的PD患者、10例未接受过药物治疗的PD患者以及按性别和年龄匹配的未受影响对照中分析了血浆miRNA水平。我们通过逆转录和定量实时PCR(RT-qPCR)评估表达水平,并使用固定效应逆方差加权荟萃分析合并接受治疗的PD患者的结果。我们揭示了血浆和WBC之间以及未接受过药物治疗和接受左旋多巴治疗的PD患者之间不同的表达谱。我们观察到接受左旋多巴治疗的PD患者中miR-30a-5p有上调趋势,并通过综合的计算机分析研究了候选靶基因。由于血浆中表达极低,我们无法分析通常在WBC中表达的miR-29b-3p。我们在WBC和血浆中观察到不同的表达谱,表明它们都是适合但不可互换的外周生物标志物来源。我们揭示了miR-30a-5p作为血浆中PD的潜在生物标志物。计算机分析表明miR-30a-5p可能在线粒体动力学和自噬中具有调节作用。需要进一步研究以确认miR-30a-5p的失调和靶标,并研究左旋多巴治疗对miRNA表达水平的影响。