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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| Vydáno v: | Frontiers in cellular neuroscience Ročník 13; s. 58 |
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| Hlavní autoři: | , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
Switzerland
Frontiers Research Foundation
22.02.2019
Frontiers Media S.A |
| Témata: | |
| ISSN: | 1662-5102, 1662-5102 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | 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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| Bibliografie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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 |