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Transcriptomics analysis of post-mortem substantia nigra samples from Parkinson’s disease patients and controls.

ABSTRACT: Transcriptomics analysis of post-mortem substantia nigra samples from Parkinson’s disease patients and controls.

PROVIDER: PRJNA707560 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13895078.fastq.gz	Fastqsanger.gz
	SRR13895079.fastq.gz	Fastqsanger.gz
	SRR13895080.fastq.gz	Fastqsanger.gz
	SRR13895081.fastq.gz	Fastqsanger.gz
	SRR13895082.fastq.gz	Fastqsanger.gz

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Transcriptional and interactome network analyses of Substantia Nigra in progressive stages of Parkinson’s disease

Project description:We analyzed the transcriptomic profile of post-mortem substantia nigra explants from controls, intermediate - Braak 3 (BK3) and 4 (BK4) - stages of Parkinson’s disease in order to investigate how gene-gene interaction patterns vary along disease development. The comparative transcriptional networks analyses indicate that the main hubs in CT network showed less gene-gene connections in BK3 and BK4 networks, probably reflecting changes in SN cell metabolism, population and density along PD stages.

2018-11-30 | GSE42966 | GEO

Transcriptomic profiling of substantia nigra and putamen in Parkinson’s disease

Project description:Transcriptomic profiling of substantia nigra and putamen in Parkinson’s disease

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Transcriptional interaction network analyses in dorsal nucleus of vagus nerve, locus coeruleus and substantia nigra in Parkinson's disease

Project description:We analyzed the transcriptomic profile of post-mortem explants from dorsal nucleus of vagus nerve, locus coeruleus and substantia nigra obtained from controls and Braak 4 (BK4) and 5 (BK5) stages of Parkinson’s disease (PD) patients in order to investigate how gene-gene interaction patterns vary along different anatomical regions in patients and controls. The comparative transcriptional networks analyses indicate that the main hubs in PD networks are related to ubquitin/proteasome, oxidative stress, neuroprotection, neurogenesis and PD associated proteins. Transcriptomic profiles of controls and Parkinson’s disease patients were compared using SAM test for LC or Wilcoxon Mann-Whitney test for SN and VA (p<0.005 and p<0.01, respectively) in order to identify differentially expressed transcripts.

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Transcriptomic profiling of substantia nigra and putamen in Parkinson’s disease

Project description:We report RNA sequencing results of human substantia nigra and putamen samples from Parkinson's disease patients and controls. Each substantia nigra sample is the result of pooling brain tissue from two individuals with the same , while each putamen sample is the result of pooling brain tissue from three individuals. We found 354 differentially expressed genes (DEGs) in the SN of PD patients compared to age-matched controls, while we observed 261 DEGs in the putamen samples. The top-enriched pathways from the SN were associated with “protein folding” and “neurotransmitter transport”, and the putamen DEGs with “synapse organization”. In summary, our data confirms the key role of protein folding and neuronal degeneration in the pathology of PD, and highlights new genes and pathways that have not yet been explored in the context of PD.

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Transcriptional interaction network analyses in dorsal nucleus of vagus nerve, locus coeruleus and substantia nigra in Parkinson's disease

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Transcriptomics analysis of post-mortem substantia nigra samples from Parkinson’s disease patients and controls.

Project description:Purpose: Parkinson’s disease (PD) is one of the most common neurological movement disorders. In the incidence and the clinical features of PD, significant gender differences have been observed. While males have a higher disease prevalence and are more frequently affected by muscle rigidity, females present more often with disabling tremors. The molecular mechanisms behind these disease-associated gender differences are still largely unknown, and a detailed understanding of the factors involved may open new avenues for pharmacological disease modification. Methods: To address this gap, we have conducted a meta-analysis of disease-associated molecular gender differences in brain transcriptomics data from PD case/control studies. We studied gender-dependent expression changes in individual genes and using systems level pathway and network analyses to identify coordinated gender-related molecular alterations. In each analysis, both gender-specific changes (significant alteration in only one gender) and gender-dimorphic changes (changes in both genders, but with opposite direction) were identified. Results: These analyses revealed significant disease-associated sex differences in immune response processes and mitochondrial pathways, and highlight regulatory factors, such as the transcription factor NR4A2, whose activity changes can explain ensuing alterations propagated through gene regulatory cascades. Overall, significant gender disparities were observed in PD-associated transcriptomic changes, resulting in coordinated modulations of molecular processes. Among the regulatory factors involved, NR4A2 has previously been reported to harbor rare mutations in familial PD and its pharmacological activation conferred neuroprotective effects in toxin-induced models of Parkinsonism. NR4A2 may therefore be of interest as a candidate target for further preclinical studies on addressing gender-related pathological features of PD.

2023-01-19 | GSE168496 | GEO

Polyomic analyses of dopaminergic neurons isolated from human substantia nigra in Parkinson’s disease: An exploratory study.

Project description:Dopaminergic neurons of the substantia nigra pars compacta selectively and progressively degenerate in Parkinson’s disease. Until now, molecular analyses of dopaminergic neurons in PD have been limited to genomic and transcriptomic approaches, whereas, to the best of our knowledge, no proteomic or combined polyomic study examining the protein profile of these neurons, is currently available. 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. Qualitative analyses confirmed that the microdissection protocol preserves the integrity of our samples and offers access to specific molecular pathways. This polyomic analysis highlighted differential expression of 52 genes and 33 proteins, including molecules of interest already known to be dysregulated in Parkinson’s disease, such as LRP2, PNMT, CXCR4, MAOA and CBLN1 genes, or the Aldehyde dehydrogenase 1 protein. On the other hand, despite the same samples were used for both analyses, correlation between RNA and protein expression was low, as exemplified by the CST3 gene encoding for the cystatin C protein. This is the first exploratory study analyzing both gene and protein expression of LMD-dissected neurons from substantia nigra pars compacta in Parkinson’s disease.

2021-12-30 | PXD024748 | Pride

Next generation sequencing reveals upregulation of the lncRNA LINC-PINT in the substantia nigra of human Parkinson's disease patients compared to control donors

Project description:Parkinson's disease (PD) is the second most common neurodegenerative disease, involving the selecive death of dopaminergic neurons in the substantia nigra pars compacta brain region. Here, we performed next generation sequencing on RNA extracted from human substantia nigra tissue. The samples, acquired from the Netherland's Brain Bank, were taken post-mortem from PD and non-PD control donors. Analysis of the data revealed an upregulation of lncRNA LINC-PINT in PD substantia nigra. LINC-PINT interracts with the Polycomb Repressive Complex 2 (PRC2), inhibiting the tracription of multiple targets. Correspondingly, analysis of the data revealed that targets of PRC2 displayed larger disease-associated differences as compared to other genes, as well as enrichment for downregulation, suggesting that the differential expression of LINC-PINT in PD effects LINC-PINT/PRC2 interaction as well.

2020-04-14 | GSE114517 | GEO

Transcriptomic profiling of mouse substantia nigra tissue by RNA-seq

Project description:Transcriptomic profiling of substantia nigra of wild type (WT) and Tpbg knockout (KO) mice (RNA-seq)

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A primate nigrostriatal atlas of neuronal vulnerability and resilience in a model of Parkinson’s disease

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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