Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson’s disease

ABSTRACT: Analysis of human dopamine (DA) from postmortem brains of 8 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. Human dopamine (DA) neurons from 8 PD and 9 control subjects were obtained. Double-stranded complementary DNA was made with a biotinylated T7(dT)-24 primer. Biotinylated complementary RNA was fragmented and hybridized to Affymetrix human genome U133_X3P 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Bin Zheng

PROVIDER: E-GEOD-24378 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.

Zheng Bin B Liao Zhixiang Z Locascio Joseph J JJ Lesniak Kristen A KA Roderick Sarah S SS Watt Marla L ML Eklund Aron C AC Zhang-James Yanli Y Kim Peter D PD Hauser Michael A MA Grünblatt Edna E Moran Linda B LB Mandel Silvia A SA Riederer Peter P Miller Renee M RM Federoff Howard J HJ Wüllner Ullrich U Papapetropoulos Spyridon S Youdim Moussa B MB Cantuti-Castelvetri Ippolita I Young Anne B AB Vance Jeffery M JM Davis Richard L RL Hedreen John C JC Adler Charles H CH Beach Thomas G TG Graeber Manuel B MB Middleton Frank A FA Rochet Jean-Christophe JC Scherzer Clemens R CR

Science translational medicine 20101001 52

Parkinson's disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson's and subclinical disease and healthy controls. We analyzed 6.8 million raw data points from nine genome-wide expression studies, and 185 laser-captured human dopaminergic neuron and sub ...[more]

PMID: 20926834

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Project description:Parkinson’s disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the human midbrain causing motor dysfunctions. The exact mechanism behind dopaminergic cell death is still not completely understood and, so far, no cure or neuroprotective treatment for PD is available. Recent studies have brought attention to the wide array of bioactive molecules produced by mesenchymal stem cells (MSCs), generally referred to as the secretome. Herein, we evaluated whether human MSCs-bone marrow derived (hBMSCs) secretome would be beneficial in a PD pre-clinical model, when compared directly with cell transplantation of hBMSCs alone. We used a 6-hydroxydpomanie (6-OHDA) rat PD model, and motor behavior was evaluated at different time points after treatments (1, 4 and 7 weeks). The impact of the treatments in the recovery of DA neurons was estimated by determining TH-positive neuronal densities in the substantia nigra and fibers in the striatum, respectively, at the end of the behavioral characterization. Furthermore, we determined the effect of the hBMSCs secretome on the neuronal survival of human neural progenitors in vitro, and characterized the secretome through proteomic-based approaches. This work demonstrates that the injection of hBMSCs secretome potentiated the histological recovery of DA neurons, when compared to transplantation of hBMSCs themselves, a fact that probably explains the improved behavioral performance of secretome-injected animals in the staircase test. Moreover, we observed that hBMSCs secretome induces higher levels of in vitro neuronal differentiation. Finally, the proteomic analysis revealed that hBMSCs secrete a variety of important exosome-related molecules such as those related with the ubiquitin-proteasome and histone systems. Overall, this work provided important insights on the potential use of hBMSCs secretome as a therapeutic tool for PD, and further confirms the importance of the secreted molecules rather than the transplantation of hBMSCs for the observed positive effects. These could be likely through normalization of defective processes in PD, namely proteostasis or altered gene transcription, which lately can lead to neuroprotective effects.

Dataset Information

Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson’s disease

Publications

PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.

Similar Datasets

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