Περίληψη:
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. © 2019 Elkouris, Kouroupi, Vourvoukelis, Papagiannakis, Kaltezioti, Matsas, Stefanis, Xilouri and Politis.
Συγγραφείς:
Elkouris, M.
Kouroupi, G.
Vourvoukelis, A.
Papagiannakis, N.
Kaltezioti, V.
Matsas, R.
Stefanis, L.
Xilouri, M.
Politis, P.K.
Λέξεις-κλειδιά:
beta tubulin; glucosylceramidase; leucine rich repeat kinase 2; long untranslated RNA; messenger RNA; microtubule associated protein 2; nuclear receptor related factor 1; parkin; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein deglycase DJ-1; PTEN Induced Kinase 1; Smad protein; synuclein; tau protein; transcription factor Pitx3; ubiquitin carboxy terminal hydrolase L1; ubiquitin thiolesterase; unclassified drug, adult; Article; autopsy; cell proliferation; cerebrospinal fluid analysis; clinical article; confocal microscopy; controlled study; dopaminergic nerve cell; female; gene expression; gene knockout; gene mutation; genetic analysis; genetic association; genetic code; genetic polymorphism; genetic regulation; genetic transcription; Hoehn and Yahr scale; human; human cell; human tissue; immunofluorescence; immunohistochemistry; male; middle aged; motor performance; nerve cell differentiation; nerve degeneration; Parkinson disease; pathogenesis; peripheral blood mononuclear cell; phenotype; real time polymerase chain reaction; reverse transcription polymerase chain reaction; SH-SY5Y cell line; signal transduction; transcriptomics; Unified Parkinson Disease Rating Scale; upregulation
