MRNA expression profiling of mitochondrial subunits in subjects with Parkinson’s disease
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ABSTRACT:
PROVIDER: PRJEB42212 | ENA |
REPOSITORIES: ENA
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Project description:Introduction: Parkinson's disease (PD), typically developing between the ages of 55 and 65 years, is a common neurodegenerative disorder caused by a progressive loss of dopaminergic neurons due to the accumulation of α-synuclein in the substantia nigra. Mitochondria are known to play a key role in cell respiratory function and bioenergetic. Indeed, mitochondrial dysfunction causes an insufficient energy production required to satisfy the needs of several organs, especially the nervous system. Material and methods: The present study explored the mRNA expression of mitochondrial DNA (mtDNA) encoded respiratory chain (RC) subunits in PD patients by using the next generation sequencing analysis (NGS) and the quantitative real-time PCR (qRT-PCR) assay for the confirmation of the NGS results. Results: All tested mitochondrial RC subunits was significantly over-expressed in subjects with PD compared to normal controls . In qRT-PCR the mean expression of all mitochondrial subunits had an expression level of at least 7 times compared to controls. Conclusion: The over-expression of mitochondrial subunits in PD subjects might be secondary to a degeneration-related alteration of the mitochondrial structure or dynamics or to the occurrence of a compensatory mechanism. The study of specific mRNA by peripheral blood mononuclear cells (PBMCs) may provide a better diagnostic frame to early detect PD cases.
2022-01-01 | E-MTAB-9950 | biostudies-arrayexpress
Project description:Mitochondrial DNA allelic substitutions in Parkinson’s disease
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Project description:Mitochondrial DNA (mtDNA) damage is considered as a possible primary cause of Parkinson’s disease (PD). To explore the issue, mtDNA sequences from whole blood were analyzed in PD patients and controls using a resequencing chip and allelic substitutions were estimated for each nucleotide position (np) along the entire mtDNA sequence. Overall, 58 np showed a different allelic distribution in the two groups; of these, 81% showed an increase of non-reference alleles in PD patients, similar to findings reported in patients with Alzheimer’s disease, albeit in reduced proportion. These results suggest that age-related neurodegenerative diseases could share a mechanism involving mtDNA.
2019-05-21 | GSE113704 | GEO
Project description:Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting ~2–3% of people over 65 years of age. Recent studies have revealed that the molecular pathogenesis of PD involves a series of pathways and neurobiological processes, such as protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, calcium homeostasis, axonal transport, and neuroinflammation, all suggesting that both the onset and course of PD is a complex multilevel and systematic process. Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) affect the pathogenesis of several diseases, such as cancers, immunological diseases, and neurodegenerative disorders, including Alzheimer’s disease and PD. Next generation sequencing provides a high-throughput method for exploring the diverse polyadenylated RNA populations. This approach allows accurate identification and quantitation of mRNAs and other non-coding RNAs, such as lncRNAs. The present study explored mRNAs and lncRNAs expression by using the next generation sequencing analysis (NGS) and the quantitative real-time PCR (qRT-PCR) assay for the confirmation of the NGS results, followed by functional analysis of the results.
2023-01-16 | E-MTAB-11326 | biostudies-arrayexpress
Project description:In this exploratory study, we used laser microdissection to extract dopaminergic neurons from 10 human SNpc samples obtained at autopsy in Parkinson’s disease patients and control subjects. Extracted RNA and proteins were identified by RNA sequencing and nano-LC-MS/MS, respectively, and the differential expression between Parkinson’s disease and control group was assessed.
2021-06-30 | GSE169755 | GEO
Project description:Improved diagnostic and prognostic biomarkers which reflect pathological progression would benefit the management of Parkinson’s disease. GPR37, also known as parkin associated endothelin-like (Pael) receptor, is an orphan G protein-coupled receptor, which has a defective parkin-mediated ubiquitination in autosomal recessive Parkinson’s disease. By means of immunoblot and mRNA determinations we detected increased GPR37 levels in postmortem substantia nigra from Parkinson’s disease subjects. We revealed the presence of the N-terminal domain of GPR37 (ecto-GPR37) in human and mouse cerebrospinal fluid (CSF). We engineered a Nanoluciferase-based ELISA to evaluate ecto-GPR37 in CSF and demonstrated the presence of ecto-GPR37 in CSF from wild-type, but not from GPR37-/-, mice. Subsequently, the relative abundance of ecto-GPR37 in CSF in healthy controls (n=48) and Parkinson’s disease (n=45) patients was assessed. Interestingly, we found that ecto-GPR37 was significantly increased (P = 0.0002) in the CSF from Parkinson’s disease patients. Importantly, mass spectrometric analysis of immunoprecipitation of GPR37 in CSF supported the analytical validity of our ELISA to measure ecto-GPR37 in human CSF. Overall, these results open exciting perspectives and encourage further systemically studies to confirm the clinical validity and utility of ecto-GPR37 as a potential Parkinson’s disease diagnostic/prognostic biomarker
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Project description:Analysis of human dopamine (DA) from postmortem brains of 8 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. Human dopamine (DA) neurons from 8 PD and 9 control subjects were obtained. Double-stranded complementary DNA was made with a biotinylated T7(dT)-24 primer. Biotinylated complementary RNA was fragmented and hybridized to Affymetrix human genome U133_X3P microarrays. The Affymetrix .CEL files were normalized to “all probe sets” in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.
2011-01-20 | E-GEOD-24378 | biostudies-arrayexpress
Project description:To get insight into systemic molecular events associated with Parkinson’s disease (PD), an age-related neurodegenerative disorder, we compared gene expression patterns of peripheral blood mononuclear cells (PBMC) derived from elderly healthy controls and from PD patients.
2012-03-20 | GSE22491 | GEO
Project description:Parkinson’s disease (PD) is the most common movement disorder in the aging population, with an estimated prevalence of 1% of people above 60 years old. More recently, PD risk genes, have been found to be regulated by the small non-coding RNAs, (microRNAs or miRNAs), and, as such, may contribute to PD development through a direct regulation on the mitochondrial and immune pathways. Many of these are influenced by epigenetic mechanisms, among which ones mediated by, miRNAs, that regulate gene expression at a post transcriptional level by binding to their 3′ un-translated region (3′ UTR) of target messenger RNAs (mRNAs) inducing mRNA degradation and translational repression. This study aimed to identify and characterize miRNA to evaluate their possible deregulation in PD patients compared to CRTL. In addition, we investigated how specific miRNAs are able to target genes and, thus, to modulate their functions in PD patient. Small RNA expression profiling was performed by next-generation sequencing in PD patients and CTRL after filtered out low-quality reads and trimming the adaptors. The obtained high-quality reads were aligned against the human genome reference.
2023-09-01 | E-MTAB-12087 | biostudies-arrayexpress