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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Veröffentlicht in:Frontiers in cellular neuroscience Jg. 13; S. 58
Hauptverfasser: Elkouris, Maximilianos, Kouroupi, Georgia, Vourvoukelis, Alexios, Papagiannakis, Nikolaos, Kaltezioti, Valeria, Matsas, Rebecca, Stefanis, Leonidas, Xilouri, Maria, Politis, Panagiotis K.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland Frontiers Research Foundation 22.02.2019
Frontiers Media S.A
Schlagworte:
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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Zusammenfassung: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.
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Edited by: José A. G. Agúndez, University of Extremadura, Spain
Reviewed by: Silvia Zucchelli, Università degli Studi del Piemonte Orientale, Italy; Dennis Qing Wang, Zhujiang Hospital, Southern Medical University, China
ISSN:1662-5102
1662-5102
DOI:10.3389/fncel.2019.00058