Altered Long Noncoding RNA Expression Precedes the Course of Parkinson’s Disease

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, researchers at Ludwig-Maximilians-Universitä 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.

Heatmap showing expression levels of lncRNAs analyzed in this study

Data were normalized according to the comparative C_T method using the three stably expressed references GAS5-family, HAR1B, and SNHG4. Low relative expression levels correspond with blue marks; high relative expression levels correspond with red marks. Donors 1 to 10 are controls; donors 11 to 30 are PD patients. Dnr donor

This is the first comprehensive analysis on lncRNAs in PD revealing significantly altered lncRNAs. Additionally, the researchers 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.