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.
Project description:The study is affiliated to the UKBEC sample of healthy human putamen and substantia nigra phenotype. The gender is from both male and female samples of the the phenotype.
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.
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.
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.
Project description:Analysis of substantia nigra from postmortem brains of 4 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra.
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.
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.
Project description:Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques. Here, aging-associated early changes in transcriptome of SNpc were investigated comparing late middle-aged (18 months old) to young (2 months old) mice.