Abstract
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder that poses serious burden to individuals and society as well. Although a number of PD associated genetic factors have been identified, the molecular mechanism of the disease so far has not been completely elucidated. Involvement of long non-coding RNAs (lncRNAs) in the pathology of neurodegenerative disorders is attracting increased interest because of the diverse mechanisms lncRNAs affect gene expression and cellular homeostasis at different levels. We aimed to test the feasibility of detecting alterations in lncRNA levels in easily accessible samples of PD patients by routine laboratory technique. By narrowing the number of selected lncRNAs implicated in neurodegeneration and increasing the number of PD samples included, we found one out of 41 lncRNAs readily detectable in increased level in peripheral blood of PD patients. We detected NEAT1 to be significantly up-regulated in PD patients in multiple comparisons. NEAT1 is the core element of nuclear paraspeckles and it plays role in regulation of transcription, mRNA and miRNA levels, mitochondrial and cellular homeostasis. Our finding is in accord with recent data demonstrating changes in the level of NEAT1 in neurons of PD patients and in several models of the disease. However, to our knowledge this is the first study to report NEAT1 up-regulation in blood of PD patients. Identification of altered expression of this lncRNA in the periphery might help to a better understanding of the mechanisms underlying PD, and can contribute to the identification of new therapeutic targets and disease markers.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting approximately 1-2% of the population over the age of 65 (Goedert, 2001)
The data we report here indicate a significant increase in Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) long non-coding RNA Alzheimer’s disease (AD) (lncRNA) level in peripheral blood cells of PD patients
Nine of these were directly linked to PD (RP11101C11.1, RP11-409K20.6, RP11-124N14.3, RP11-79P5.3, AC004744.3, RP11-542K23.9, PCA3 (Soreq et al, 2014), NEAT1 (Kraus et al, 2017; Simchovitz et al, 2019) and Metastasis Associated Lung Adenocarcinoma Transcript 1 SNGH1 (MALAT1) (Liu et al, 2017)), while others were associated with AD (BC200, BACE1-AS (Feng et al, 2018; Lukiw et al, 1992)), Huntington’s disease (HD) (MEG3, TUG1 (Taurine Up-Regulated Gene 1), LINC00341, HAR-1A (Chanda et al, 2018; Johnson, 2012; Johnson et al, 2010; Wang et al, 2014)), and/or were found to be involved in mechanisms that are likely related to neurodegeneration
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting approximately 1-2% of the population over the age of 65 (Goedert, 2001). Q. Wang et al, 2018) possible connections between specific non-coding transcripts and PD have been suggested: Soreq et al investigated the lncRNA profile of PD patients’ leukocytes by whole transcriptome sequencing (Soreq et al, 2014). They found that over 6000 detected leukocyte lncRNAs, 13 had altered expression in PD patients as compared to healthy controls. The overexpression of the UCHL1 protein has a neuroprotective effect, the increased expression of Uchl AS can be part of a cell-salvage mechanism (Carrieri et al, 2015)
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