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Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00058

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

  • 1Biomedical Research Foundation of the Academy of Athens, Greece
  • 2Pasteur Hellenic Institute, Greece

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 SNCA, LRRK2, PINK1, DJ-1, UCH-L1, MAPT and GBA1, are expressed in human dopaminergic cells and post-mortem material, such as cortex, Substantia Nigra 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, SNCA mRNA levels are increased in the nigra, while LRRK2 and PINK1 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.

Keywords: long-non coding RNAs, Parkinson’s disease, alpha-Synuclein, LRRK2, Substantia Nigra, Exosomes

Received: 08 Sep 2018; Accepted: 05 Feb 2019.

Edited by:

José A. Agúndez, Institute of Molecular Pathology Biomarkers, University of Extremadura, Spain

Reviewed by:

Silvia Zucchelli, University of Eastern Piedmont, Italy
Dennis Qing Wang, Zhujiang hospital, Southern Medical University, China  

Copyright: © 2019 Elkouris, Kouroupi, Vourvoukelis, Papagiannakis, Kaltezioti, Matsas, Stefanis, Xilouri and Politis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Maria Xilouri, Biomedical Research Foundation of the Academy of Athens, Athens, Greece,
Dr. Panagiotis Politis, Biomedical Research Foundation of the Academy of Athens, Athens, Greece,