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 numb...

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Published in:	Frontiers in cellular neuroscience Vol. 13; p. 58
Main Authors:	Elkouris, Maximilianos, Kouroupi, Georgia, Vourvoukelis, Alexios, Papagiannakis, Nikolaos, Kaltezioti, Valeria, Matsas, Rebecca, Stefanis, Leonidas, Xilouri, Maria, Politis, Panagiotis K.
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Research Foundation 22.02.2019 Frontiers Media S.A
Subjects:	alpha-synuclein Biomedical research Brain research Cardiovascular disease Cell differentiation Cerebellum Cerebrospinal fluid Dopamine receptors Exosomes Gene expression Genomes Ischemia Leukocytes (mononuclear) long-non coding RNAs LRRK2 LRRK2 protein Medical prognosis MicroRNAs Movement disorders Neurodegeneration Neurodegenerative diseases Neurogenesis Neurological diseases Neuroscience Neurosciences Non-coding RNA PARK7 protein Parkinson's disease Pathogenesis Peripheral blood mononuclear cells Pluripotency Protein synthesis Proteins PTEN-induced putative kinase Stem cells Studies Substantia Nigra Transcription Greece alpha-synuclein Substantia Nigra LRRK2 exosomes Parkinson’s disease long-non coding RNAs
ISSN:	1662-5102, 1662-5102
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Abstract	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 , , , , , and , are expressed in human dopaminergic cells and post-mortem material, such as cortex, 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, mRNA levels are increased in the nigra, while and 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.
AbstractList	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.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. 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. 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 , , , , , and , are expressed in human dopaminergic cells and post-mortem material, such as cortex, 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, mRNA levels are increased in the nigra, while and 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.
Author	Kouroupi, Georgia Stefanis, Leonidas Elkouris, Maximilianos Kaltezioti, Valeria Xilouri, Maria Politis, Panagiotis K. Vourvoukelis, Alexios Papagiannakis, Nikolaos Matsas, Rebecca
AuthorAffiliation	4 First Department of Neurology, National and Kapodistrian University of Athens Medical School , Athens , Greece 3 Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens , Athens , Greece 1 Center for Basic Research, Biomedical Research Foundation of the Academy of Athens , Athens , Greece 2 Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute Athens , Greece
AuthorAffiliation_xml	– name: 3 Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens , Athens , Greece – name: 2 Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute Athens , Greece – name: 1 Center for Basic Research, Biomedical Research Foundation of the Academy of Athens , Athens , Greece – name: 4 First Department of Neurology, National and Kapodistrian University of Athens Medical School , Athens , Greece
Author_xml	– sequence: 1 givenname: Maximilianos surname: Elkouris fullname: Elkouris, Maximilianos – sequence: 2 givenname: Georgia surname: Kouroupi fullname: Kouroupi, Georgia – sequence: 3 givenname: Alexios surname: Vourvoukelis fullname: Vourvoukelis, Alexios – sequence: 4 givenname: Nikolaos surname: Papagiannakis fullname: Papagiannakis, Nikolaos – sequence: 5 givenname: Valeria surname: Kaltezioti fullname: Kaltezioti, Valeria – sequence: 6 givenname: Rebecca surname: Matsas fullname: Matsas, Rebecca – sequence: 7 givenname: Leonidas surname: Stefanis fullname: Stefanis, Leonidas – sequence: 8 givenname: Maria surname: Xilouri fullname: Xilouri, Maria – sequence: 9 givenname: Panagiotis K. surname: Politis fullname: Politis, Panagiotis K.
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Copyright	2019. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Copyright © 2019 Elkouris, Kouroupi, Vourvoukelis, Papagiannakis, Kaltezioti, Matsas, Stefanis, Xilouri and Politis. 2019 Elkouris, Kouroupi, Vourvoukelis, Papagiannakis, Kaltezioti, Matsas, Stefanis, Xilouri and Politis
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Keywords	alpha-synuclein Substantia Nigra LRRK2 exosomes Parkinson’s disease long-non coding RNAs
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SubjectTerms	alpha-synuclein Biomedical research Brain research Cardiovascular disease Cell differentiation Cerebellum Cerebrospinal fluid Dopamine receptors Exosomes Gene expression Genomes Ischemia Leukocytes (mononuclear) long-non coding RNAs LRRK2 LRRK2 protein Medical prognosis MicroRNAs Movement disorders Neurodegeneration Neurodegenerative diseases Neurogenesis Neurological diseases Neuroscience Neurosciences Non-coding RNA PARK7 protein Parkinson's disease Pathogenesis Peripheral blood mononuclear cells Pluripotency Protein synthesis Proteins PTEN-induced putative kinase Stem cells Studies Substantia Nigra Transcription
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Title	Long Non-coding RNAs Associated With Neurodegeneration-Linked Genes Are Reduced in Parkinson’s Disease Patients
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