CircRNAs microarray analysis in plasma of Parkinson’s Disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE174052 | GEO | 2023/05/01
REPOSITORIES: GEO
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Project description:The degenerative process in Parkinson’s disease (PD) causes a progressive loss of dopaminergic neurons (DaNs) in the nigrostriatal system. Resolving the differences in neuronal susceptibility warrants an amenable PD model that, in comparison to post-mortem human specimens, controls for environmental and genetic differences in PD pathogenesis. At present study, we generated a primate model of PD by carotid artery injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP and sampled substantia nigra and putamen of macaque for single cell sequencing analysis.
2023-11-19 | E-MTAB-13437 | biostudies-arrayexpress
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2020-03-26 | PXD015239 | Pride
Project description:The molecular mechanism underlying Parkinson's disease (PD), an increasingly common neurodegenerative disease, remains unclear. Long non-coding RNA (lncRNA) plays essential roles in gene expression and human disease. We hypothesize that lncRNAs are involved in the pathogenesis of PD. We profiled the expression of lncRNA in circulating leukocytes of 5 PD patients and 5 healthy controls using microarray.
2019-12-04 | GSE133347 | GEO
Project description:Detailed analysis of disease-affected tissue provides insight into molecular mechanisms contributing to pathogenesis. Substantia nigra, striatum and cortex are functionally connected with increasing degrees of alpha-synuclein pathology in Parkinson's disease. Functional and causal pathway analysis of gene expression and proteomic alterations in these three regions revealed pathways that correlated with deposition of alpha-synuclein. Microarray and RNAseq experiments revealed previously unidentified causal changes related to oligodendrocyte function and synaptic vesicle release and other changes were reflected across all brain regions. Importantly a subset of these changes were replicated in Parkinson's disease blood. Proteomic assessment revealed alterations in mitochondria and vesicular transport proteins that preceded gene gene expression changes indicating defects in translation and/or protein turnover. Our combined approach of proteomics, RNAseq and microarray analyses provides a comprehensive view of the molecular changes that accompany alpha-synculein pathology in Parkinson's disease, and may be instrumental in understanding and diagnosing Parkinson's disease progression. Substantia Nigra (3 normal, 3 PD), Striatum (6 normal, 6 PD), Cortex (5 normal, 5 PD), Cortex non-PD neurodegeneration (2 normal, 3 DLB). Note Sample X201264 was used both for Cortex normal and for Cortex nonPD normal
2014-09-01 | E-GEOD-54282 | biostudies-arrayexpress
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.
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2008-11-22 | E-GEOD-6613 | biostudies-arrayexpress
Project description:Parkinson's disease (PD) is a growing burden worldwide, and despite ongoing efforts to find reliable biomarkers for early and differential diagnosis, prognosis and disease monitoring, there is no biofluid biomarker used in clinical routine to date. Cerebrospinal fluid (CSF) is collected often and should closely reflect structural and functional alterations in PD patients' brains. Here we describe a scalable and sensitive mass spectrometry (MS)-based proteomics workflow for CSF proteome profiling to find specific biomarkers and identify disease-related changes in CSF protein levels in PD. From two independent cohorts consisting of more than 200 individuals, our workflow reproducibly quantified over 1,700 proteins from minimal sample amounts. Combined with machine learning, this identified a group of several proteins, including OMD, CD44, VGF, PRL, and MAN2B1 that were altered in PD patients or significantly correlate with clinical scores, indicative of disease progression. Interestingly, we uncovered signatures of enhanced neuroinflammation in patients with familial PD (LRRK2 G2019S carriers) as indicated by increased levels of CTSS, PLD4, HLA-DRA, HLA-DRB1, and HLA-DPA1. A comparison with urinary proteome changes in PD patients revealed a large overlap in protein composition PD-associated changes in these body fluids, including lysosomal factors like CTSS. Our results validate MS-based proteomics of CSF as a valuable strategy for biomarker discovery and patient stratification in a neurodegenerative disease like PD. Consistent proteomic signatures across two independent CSF cohorts and previously acquired urinary proteome profiles open up new avenues to improve our understanding of PD pathogenesis.
2022-06-01 | PXD026491 | Pride
Project description:Parkinson’s disease (PD) involves myriad genetic, behavioral, and environmental factors that make the identification of effective therapeutic targets challenging. We leverage a novel, validated AI approach to identify cell type- and brain region-specific epigenomic features in 6 brain regions from 35 individuals with varying genetic risk for PD as well as clinical and pathological controls (CTRL, n=15). We observed that astrocytes of substantia nigra (SUNI) are the major regional and cellular site of differentially accessible regions (DARs) between sporadic PD (SPOR_PD+, n=15) and GBA1 mutation-carriers with PD (GBA1_PD+, n=16); Seven of these SUNI DARs not only fully separated SPOR_PD+ from GBA1_PD+ cases but could also fully separate LRRK2 mutation carriers with PD from these other two forms of PD (n=3). Molecular estimation of PD progression, which correlated with the progression of neuropathologic stage, reveals that chromatin differences between SPOR_PD+ and GBA1_PD+ increase along the predicted disease progression, with broad cell type significant differences in epigenomic profiles at predicted later stages of the disease. Having APOE 4 (n=14 cases) was shown to affect various cell types mainly in the superior and middle temporal gyrus and substantial nigra. Using a multicellular co-accessibility network analysis, we identify neuron-specific epigenomic modules that correlate with the presence of at least one APOE 4 and the increase of PD pathological and clinical phenotypes. Our results suggest that APOE 4 could contribute to PD pathogenesis through chromatin change in neural cells related to synaptic and neuronal projection processes. This study expands our understanding of genetic risk effects in Parkinson's disease and provides a blueprint framework for investigating the cellular basis of genetic risk effects in disease.
2024-07-30 | GSE273511 | GEO
Project description:The prevalence of Parkinson's disease (PD) is increasing but the development of novel treatment strategies and therapeutics altering the course of the disease would benefit from specific, sensitive and non-invasive biomarkers to detect PD early. Here, we describe a scalable and sensitive proteomics workflow for urinary proteome profiling by combining high-throughput sample preparation with state-of-the-art mass spectrometry (MS)-based proteomics. Our workflow enabled the reproducible quantification of more than 2,000 proteins in more than 200 urine samples using minimal volumes from two independent cohorts. The urinary proteome was significantly different between PD patients and healthy controls as well as between LRRK2 G2019S carriers and non-carriers in both cohorts. Interestingly, our data revealed lysosomal dysregulation in individuals with the LRRK2 G2019S mutation. Machine learning on the urinary proteome data alone classified mutation status and especially disease manifestation in mutation carriers remarkably well (ROC AUCs 0.87 and 0.94, respectively), identifying VGF, ENPEP and other PD-associated proteins as the most discriminating features. Our results validate urinary proteomics as a valuable strategy for biomarker discovery and patient stratification in PD.
2020-11-24 | PXD020722 | Pride
Project description:Parkinson's disease (PD) is a neurodegenerative disease characterized by bradycardia, static tremor, rigidity and postural instability. At present, the current knowledge remains inadequate for the connection between the disease severity and peripheral immune response. In the present study, using single-cell RNA sequencing (scRNA-seq), we profiled peripheral blood mononuclear cells (PBMCs) from clinical cases, including 2 early PD, 2 advance PD and 2 matched controls, representing five major immune cell subsets: T cells (CD4+, CD8+), monocytes, B cells, natural killer (NK) cells and hematopoietic stem cells (HSCs). The characteristic alterations of cell subset proportions were disentangled, in which T cells and NK cells were declined in the progression of PD. We further enlarged the sample size and collected peripheral blood samples of 14 normal individuals, 21 early and 14 advance PD patients. T cells and NK cells showed an obvious reduction in the blood samples as the disease proceeded. Moreover, NK cells infiltration into cerebral motor cortex indicated by immunostaining of human brain sections evidenced the close communication existing between peripheral immune response and central nervous system. Importantly, NK cells participated in numerous common immune-related biological processes. Strikingly, NK cell-specific XCL2 that was specifically expressed in cluster 6 was further identified and positively correlated with the PD severity. All these findings delineated the critical role of peripheral adaptive immune response, especially mediated by NK cells, in the pathogenesis of PD, providing clues of immune-related biomarkers or therapeutic targets during PD progression in future investigations.
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