Project description:Autophagy is a highly conserved degradation pathway whereby not only cytosolic components but also aberrant proteins are sequestered within double-membraned vesicles. Parkinson's disease (PD) is pathologically characterized by accumulation of phosphorylated α-synuclein in the neuronal cytoplasm and its accumulation occurs in the peripheral autonomic nervous system as well as the central nervous system. In the brains of patients with PD, abnormal autophagy is known to occur and be involved with neurodegeneration. To investigate abnormal autophagy in peripheral blood mononuclear cells (PBMC) in the patients with PD, we performed whole transcriptome analysis of PBMC obtained from 9 normal controls and 10 patients with PD.

2017-07-27 | GSE100054 | GEO

Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 3

Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Analysis of substantia nigrae from postmortem brains of 6 patients with Parkinson's disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. Substantia nigra samples from 6 PD and 5 control subjects were obtained. At autopsy, brain hemispheres were frozen in liquid nitrogen and stored at -80C in the Kathleen Price Bryan Brain Bank in the Alzheimer's Disease Research Center at Duke University. Using the RNAgents kit (Promega, Madison, Wis), RNA was extracted from SN and adjacent midbrain tissues. Double-stranded complementary DNA was made with a biotinylated T7(dT)-24 primer. Twenty micrograms of biotinylated complementary RNA was fragmented and hybridized to Affymetrix human genome U133A 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-20164 | biostudies-arrayexpress

Mass spectrometry-based proteomics analysis of human substantia nigra from Parkinson's disease patients identifies multiple pathways potentially involved in the disease

Project description:Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) of the brain. Despite decades of studies, the precise pathogenic mechanism of PD is still elusive. An unbiased proteomic analysis of PD patients’ brains allows the identification of critical proteins and molecular pathways that lead to dopamine cell death and α-synuclein deposition and the resulting devastating clinical symptoms. In this study, we conducted an in-depth proteome analysis of human SN tissues from 15 PD patients and 15 healthy control (HC) individuals combining Orbitrap mass spectrometry with the isobaric tandem mass tag (TMT)-based multiplexing technology. We identified 10,040 proteins with 1,140 differentially expressed proteins in the SN of PD patients. Pathway analysis showed that the ribosome pathway was the most enriched one, followed by GABAergic synapse, retrograde endocannabinoid signaling, cell adhesion molecules (CAMs), morphine addiction, Prion disease, and Parkinson's disease pathways. Strikingly, the majority of the proteins enriched in the ribosome pathway were mitochondrial ribosomal proteins (mitoribosomes; MRPs). The subsequent protein-protein interaction (PPI) analysis and the weighted gene co-expression network analysis (WGCNA) confirmed that the mitoribosome is the most enriched protein cluster. Furthermore, the mitoribosome was also identified in our analysis of a replication set of 10 PD and 9 HC SN tissues. This study provides potential disease pathways involved in PD and paves the way to study further the pathogenic mechanism of PD.

2022-12-08 | PXD037684 | Pride

Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 2

Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Examination of substantia nigra from postmortem brains of 8 patients with Parkinson's disease (PD). The substantia nigra samples from 8 PD subjects were obtained from the Human Brain and Spinal Fluid Resource Center, VAMC, Los Angeles, CA, the Mind Unit Brain Bank at the University of Rochester, Rochester, NY, and from Dr. E. Masliah at UCSD, San Diego, CA, and 9 control subjects were obtained from the University of Rochester Alzheimer's Disease Center brain bank. The RNA was extracted using Trizol reagent (Invitrogen), DNAse treated with Qiagen DNAse, and analyzed on a bioanalyzer. The complementary RNA was fragmented and hybridized to Affymetrix human U133A arrays. The total 17 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-20163 | biostudies-arrayexpress

Presence of bacterial infection in brains of patients with Parkinson's disease (PD)

Project description:Isolation of bacteria in infected brains in patients with Parkinson's disease. Here we used next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis).

| EGAS00001003643 | EGA

Transcription profiling of human patients with Parkinsons disease (50), 33 patients with neurodegenerative diseases other than PD, and 23 healthy controls

Project description:Parkinson's disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular marker here identified is strongly associated with risk of PD in 66 samples of the training set (third tertile cross-validated odds ratio of 5.7 {P for trend 0.005}). It is further validated in 39 independent test samples (third tertile odds ratio of 5.1 {P for trend 0.04}). The genes differentially expressed in patients with PD, or Alzheimer's or progressive supranuclear palsy offer unique insights into disease-linked processes detectable in peripheral blood. Combining gene expression scans in blood and linked clinical data will facilitate the rapid characterization of candidate biomarkers as demonstrated here with respect to PD. Experiment Overall Design: Whole blood expression data from 50 patients with Parkinson's disease, 33 with neurodegenerative diseases other than PD, and 23 healthy controls.

2008-11-22 | E-GEOD-6613 | biostudies-arrayexpress

Gene Expression in the Blood of Parkinson's Disease Patients

Project description:Peripheral blood was collected from 18 Parkinson's Disease (PD) patients and 12 healthy controls (Ctrls). Total RNA was isolated and hybridized onto Affymetrix Exon_ST1 arrays to find in PDs versus controls: 1) genes that are differentiallly expressed and 2) genes with differential exonic expression (alternative splicing).

2010-02-04 | GSE18838 | GEO

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