AUTHOR=Elkouris Maximilianos , Kouroupi Georgia , Vourvoukelis Alexios , Papagiannakis Nikolaos , Kaltezioti Valeria , Matsas Rebecca , Stefanis Leonidas , Xilouri Maria , Politis Panagiotis K. 

TITLE=Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson’s Disease Patients

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00058

DOI=10.3389/fncel.2019.00058

ISSN=1662-5102

ABSTRACT=<p>Transcriptome analysis has identified a plethora of long non-coding RNAs (lncRNAs) expressed in the human brain and associated with neurological diseases. However, whether lncRNAs expression levels correlate with Parkinson’s disease (PD) pathogenesis remains unknown. Herein, we show that a number of lncRNA genes encompassing transcriptional units in close proximity to PD-linked protein-coding genes, including <italic>SNCA</italic>, <italic>LRRK2</italic>, <italic>PINK1</italic>, <italic>DJ-1</italic>, <italic>UCH-L1</italic>, <italic>MAPT</italic> and <italic>GBA1</italic>, are expressed in human dopaminergic cells and post-mortem material, such as cortex, <italic>Substantia Nigra</italic> and cerebellum. Interestingly, these lncRNAs are upregulated during neuronal differentiation of SH-SY5Y cells and of dopaminergic neurons generated from human fibroblast-derived induced pluripotent stem cells. Importantly, six lncRNAs are found under-expressed in the nigra and three in the cerebellum of PD patients compared to controls. Simultaneously, <italic>SNCA</italic> mRNA levels are increased in the nigra, while <italic>LRRK2</italic> and <italic>PINK1</italic> mRNA levels are decreased both in the nigra and the cerebellum of PD subjects compared to controls, indicating a possible correlation between the expression profile of the respective lncRNAs with their adjacent coding genes. Interestingly, all dysregulated lncRNAs are also detected in human peripheral blood mononuclear cells and four of them in exosomes derived from human cerebrospinal fluid, providing initial evidence for their potential use as diagnostic tools for PD. Our data raise the intriguing possibility that these lncRNAs may be involved in disease pathogenesis by regulating their neighboring PD-associated genes and may thus represent novel targets for the diagnosis and/or treatment of PD or related diseases.</p>