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.
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).
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.
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.
Project description:Voxelation is a novel technology designed to produce high throughput, three-dimensional imaging of gene expression patterns in the brain. In these experiments, mouse brains were dissected into 40 voxels, or cubes, by cutting 10 serial coronal sections and transecting each coronal section into fourths. Using microarrays, the gene expression pattern of 9000 genes was acquired for both a normal and a pharmacological model of Parkinson's disease (PD) mouse brain. The mice used in these experiments were C57BL/6J males 10-24 weeks in age. Keywords = voxelation, 3-D gene expression, Parkinson's disease Keywords: other
Project description:Parkinson's Disease (PD) and Non-Demented Control (NDC) human sera were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. In the study presented here, 29 PD and 40 NDC human serum samples were probed onto human protein microarrays in order to identify differentially expressed autoantibodies. Microarray data was analyzed using several statistical significance algorithms, and autoantibodies that demonstrated significant group prevelance were selected as biomarkers of disease. Prediction classification analysis tested the diagnostic efficacy of the identified biomarkers; and differentiation of PD samples from other neurodegeneratively-diseased and non-neurodegeneratively-diseased controls (Alzheimer's disease, multiple sclerosis, and breast cancer) confirmed their specificity.
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
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.
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.