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

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

PROVIDER: PRJNA717801 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14084326.fastq.gz	Fastqsanger.gz
	SRR14084327.fastq.gz	Fastqsanger.gz
	SRR14084328.fastq.gz	Fastqsanger.gz
	SRR14084329.fastq.gz	Fastqsanger.gz
	SRR14084330.fastq.gz	Fastqsanger.gz

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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

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

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

RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain

Project description:RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain

2015-07-27 | GSE64452 | GEO

RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain

Project description:RNA-SEQ profiling of dopaminergic neurons from the substantia nigra pars compacta and ventral tegmental area regions of the mouse mid-brain Murine midbrain dopaminergic neurons from the SNpc and VTA regions

2015-07-27 | E-GEOD-64452 | biostudies-arrayexpress

Transcription profiling of dopaminergic neurons of the substantia nigra pars compacta (SNc) and the ventral tegmental area from normal rats

Project description:The cardinal clinical features of Parkinson's disease result from selective loss of midbrain dopaminergic neurons. The goal of this experiment is to determine the gene expression profiles of these neurons by studying untreated rat substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopaminergic neurons using laser capture microscopy to obtain region-specific neuronal mRNA.

2007-10-27 | E-GEOD-1157 | biostudies-arrayexpress

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.

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Ca2+ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons

Project description:How do neurons match generation of adenosine triphosphate (ATP) by mitochondria to the bioenergetic demands of regenerative activity? Although the subject of speculation, this coupling is still poorly understood, particularly in neurons that are tonically active. To help fill this gap, pacemaking substantia nigra dopaminergic neurons were studied using a combination of optical, electrophysiological and molecular approaches. In these neurons, spike-activated calcium (Ca2+) entry through Cav1 channels triggered Ca2+ release from the endoplasmic reticulum, which stimulated mitochondrial OXPHOS through two complementary Ca2+-dependent mechanisms: one mediated by the mitochondrial uniporter and another by the malate-aspartate shuttle. Disrupting either mechanism impaired the ability of dopaminergic neurons to sustain spike activity. While this feedforward control helps dopaminergic neurons meet the bioenergetic demands associated with sustained spiking, it also is responsible for their elevated oxidant stress and possibly to their decline with aging and disease.

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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.

2020-09-02 | GSE136666 | 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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Proteomic characterization of synaptosomes from human substantia nigra indicates altered mitochondrial translation in Parkinson’s disease

Project description:Parkinson´s disease (PD) feature a progressive degeneration of dopaminergic neurons in the substantia nigra (SN). Additionally, numerous studies indicate an altered synaptic function during the course of PD. In order to characterize the proteome of synaptosomes isolated from the substantia nigra and to gain new insights into the molecular processes underlying the alteration of synaptic function in PD, a proteomic study was conducted. Synaptosomes were isolated from substantia nigra tissue of control subjects free of pathology (N = 5) and individuals at advanced PD stages (N = 5) by density gradient centrifugation and further analyzed by mass spectrometry. 362 proteins were identified and assigned to the synaptosomal core proteome. This core proteome includes all proteins expressed within the synapses without regards to data analysis software, gender, age or disease. The CD9 antigen was overrepresented and fourteen proteins, among them Thymidine kinase 2 (TK2), mitochondrial, 39S ribosomal protein L37, mitochondrial,, Neurolysin, and Methionine-tRNA ligase, mitochondrial (MARS2)) were underrepresented suggesting an alteration in mitochondrial translation in PD synaptosomes.

2021-06-07 | PXD022092 | Pride

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