Center for Neuropathology and Prion Research (ZNP), Ludwig-Maximilians-Universität, Feodor-Lynen-Str. 23, 81377, Munich, Bavaria, Germany.
Mol Neurobiol. 2017 May;54(4):2869-2877. doi: 10.1007/s12035-016-9854-x. Epub 2016 Mar 28.
Parkinson's disease (PD) is a slowly progressing neurodegenerative disorder that affects approximately seven million patients worldwide. Despite intensive research, the molecular mechanisms initiating and promoting PD are still unknown. However, it is assumed that environmental factors trigger PD. Recent research demonstrated that long noncoding RNAs (lncRNA) interfere in transcriptional and translational processes modulating gene expression reflecting environmental influences. Nevertheless, there is no systematic analysis available that investigates the impact of lncRNAs on PD. In the current study, we performed a comprehensive analysis on expression levels of 90 well-annotated lncRNAs in 30 brain specimens deriving from 20 PD patients and 10 controls as a preliminary report on the significance of lncRNAs in PD. Expression profiling of lncRNAs revealed that five lncRNAs are significantly differentially expressed in PD. While H19 upstream conserved 1 and 2 is significantly downregulated in PD, lincRNA-p21, Malat1, SNHG1, and TncRNA are significantly upregulated. An analysis on expression levels and PD stages revealed that the identified dysregulated lncRNA are altered already in early disease stage and that they precede the course of PD. In summary, this is the first comprehensive analysis on lncRNAs in PD revealing significantly altered lncRNAs. Additionally, we found that lncRNA dysregulations precede the course of the disease. Thus, the five newly identified lncRNAs may serve as potential new biomarkers appropriate even in early PD. They may be used in monitoring disease progression and they may serve as potential new targets for novel therapeutic approaches.
帕金森病(PD)是一种进展缓慢的神经退行性疾病,全球约有 700 万患者。尽管进行了深入研究,但引发和促进 PD 的分子机制仍不清楚。然而,人们认为环境因素会引发 PD。最近的研究表明,长非编码 RNA(lncRNA)干扰转录和翻译过程,调节反映环境影响的基因表达。然而,目前还没有系统的分析来研究 lncRNA 对 PD 的影响。在本研究中,我们对 30 个脑标本中的 90 个经过充分注释的 lncRNA 的表达水平进行了全面分析,这些脑标本来自 20 名 PD 患者和 10 名对照者,这是关于 lncRNA 在 PD 中的意义的初步报告。lncRNA 表达谱分析显示,5 个 lncRNA 在 PD 中表达差异显著。H19 上游保守区 1 和 2 在 PD 中显著下调,而 lincRNA-p21、Malat1、SNHG1 和 TncRNA 则显著上调。对表达水平和 PD 分期的分析表明,鉴定出的失调 lncRNA 已经在疾病早期阶段发生改变,并且它们先于 PD 的病程。总之,这是 PD 中 lncRNA 的首次全面分析,揭示了明显改变的 lncRNA。此外,我们发现 lncRNA 失调先于疾病的发生。因此,这 5 个新鉴定的 lncRNA 可能作为潜在的新生物标志物,甚至在早期 PD 中也适用。它们可用于监测疾病进展,也可作为新的治疗方法的潜在新靶点。