Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson’s Disease Patients
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00058/full |
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| author | Maximilianos Elkouris Georgia Kouroupi Alexios Vourvoukelis Nikolaos Papagiannakis Nikolaos Papagiannakis Valeria Kaltezioti Rebecca Matsas Leonidas Stefanis Leonidas Stefanis Maria Xilouri Panagiotis K. Politis |
| author_facet | Maximilianos Elkouris Georgia Kouroupi Alexios Vourvoukelis Nikolaos Papagiannakis Nikolaos Papagiannakis Valeria Kaltezioti Rebecca Matsas Leonidas Stefanis Leonidas Stefanis Maria Xilouri Panagiotis K. Politis |
| author_sort | Maximilianos Elkouris |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T06:44:04Z |
| format | Article |
| id | doaj.art-3bbbd21ae1e346fea48273fd657b1a42 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-20T06:44:04Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-3bbbd21ae1e346fea48273fd657b1a422022-12-21T19:49:46ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-02-011310.3389/fncel.2019.00058423866Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson’s Disease PatientsMaximilianos Elkouris0Georgia Kouroupi1Alexios Vourvoukelis2Nikolaos Papagiannakis3Nikolaos Papagiannakis4Valeria Kaltezioti5Rebecca Matsas6Leonidas Stefanis7Leonidas Stefanis8Maria Xilouri9Panagiotis K. Politis10Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, GreeceLaboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur InstituteAthens, GreeceCenter of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, GreeceCenter of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, GreeceFirst Department of Neurology, National and Kapodistrian University of Athens Medical School, Athens, GreeceCenter for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, GreeceLaboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur InstituteAthens, GreeceCenter of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, GreeceFirst Department of Neurology, National and Kapodistrian University of Athens Medical School, Athens, GreeceCenter of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, GreeceCenter for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, GreeceTranscriptome 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.https://www.frontiersin.org/article/10.3389/fncel.2019.00058/fulllong-non coding RNAsParkinson’s diseasealpha-synucleinLRRK2Substantia Nigraexosomes |
| spellingShingle | Maximilianos Elkouris Georgia Kouroupi Alexios Vourvoukelis Nikolaos Papagiannakis Nikolaos Papagiannakis Valeria Kaltezioti Rebecca Matsas Leonidas Stefanis Leonidas Stefanis Maria Xilouri Panagiotis K. Politis Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson’s Disease Patients Frontiers in Cellular Neuroscience long-non coding RNAs Parkinson’s disease alpha-synuclein LRRK2 Substantia Nigra exosomes |
| title | Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson’s Disease Patients |
| title_full | Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson’s Disease Patients |
| title_fullStr | Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson’s Disease Patients |
| title_full_unstemmed | Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson’s Disease Patients |
| title_short | Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson’s Disease Patients |
| title_sort | long non coding rnas associated with neurodegeneration linked genes are reduced in parkinson s disease patients |
| topic | long-non coding RNAs Parkinson’s disease alpha-synuclein LRRK2 Substantia Nigra exosomes |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00058/full |
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