Dataset Information

Gene expression profiling analysis of the putamen for the investigation of compensatory mechanisms in Parkinson's disease.

ABSTRACT: Parkinson's disease (PD) is affecting 5 million people worldwide, but the response mechanisms of the striatum are still unclear. Therefore, identification of gene expression alterations in the striatum will greatly assist the development of novel therapy strategies.We performed a comprehensive gene expression analysis in 15 PD patients and 15 normal controls to identify differentially expressed genes (DEGs) using the expression profile GSE20291 from Gene Expression Omnibus (GEO). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were used to define functions and pathways altered in PD. Protein-protein interaction network was constructed to find out the modules with close interactions.Total715 DEGs including 268 up-regulated and 447 down-regulated genes were obtained. GO functional enrichment analysis indicated that the genes related with neurons function and cell morphogenesis might be changed upon PD. KEGG pathway enrichment analysis showed that most of the genes were enriched in the nodes of Gap junction, calcium signaling pathway, phosphatidylinositol signaling system, long-term potentiation, Alzheimer's disease and GnRH signaling pathway. Protein-protein interaction network and module analysis suggested that some apoptosis related genes, such as PRKCA, CDC42 and BCL2 may play critical roles in striatal neurons growth.Intrinsic striatal tyrosine hydroxylase interneurons growth may be promoted by changes in several genes expression and thus reduce the functional excitatory synapses.

SUBMITTER: Gao L

PROVIDER: S-EPMC4225573 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gene expression profiling analysis of the putamen for the investigation of compensatory mechanisms in Parkinson's disease.

Gao Lianbo L Gao Honghua H Zhou Huan H Xu Yanyuan Y

BMC neurology 20131120

<h4>Background</h4>Parkinson's disease (PD) is affecting 5 million people worldwide, but the response mechanisms of the striatum are still unclear. Therefore, identification of gene expression alterations in the striatum will greatly assist the development of novel therapy strategies.<h4>Methods</h4>We performed a comprehensive gene expression analysis in 15 PD patients and 15 normal controls to identify differentially expressed genes (DEGs) using the expression profile GSE20291 from Gene Expres ...[more]

PMID: 24256571

Similar Datasets

Project description:Parkinson´s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Aggravation of symptoms is mirrored by accumulation of protein aggregates mainly composed by alpha-synuclein in different brain regions, called Lewy bodies (LB). Previous studies have identified several molecular mechanisms as autophagy and inflammation playing a role in PD pathogenesis. Increased insights into mechanisms involved in early disease stages and driving the progression of the LB pathology are required for the development of disease-modifying strategies. Here, we aimed to elucidate disease stage-specific transcriptomic changes in brain tissue of well-characterized PD and control donors. We collected frontal cortex samples from 84 donors and sequenced both the coding and non-coding RNAs. We categorized our samples into groups based on their degree of LB pathology aiming to recapitulate a central aspect of disease progression. Using an analytical pipeline that corrected for sex, age at death, RNA quality, cell composition and unknown sources of variation, we found major disease stage-specific transcriptomic changes. Gene expression changes were most pronounced in donors at the disease stage when microscopic LB changes first occur in the sampled brain region. Additionally, we identified disease stage-specific enrichment of brain specific pathways and immune mechanisms. On the contrary, we showed that mitochondrial mechanisms are enriched throughout the disease course. Our data-driven approach also suggests a role for several poorly characterized lncRNAs in disease development and progression of PD. Finally, by combining genetic and epigenetic information, we highlighted two genes (MAP4K4 and PHYHIP) as candidate genes for future functional studies. Together our results indicate that transcriptomic dysregulation and associated functional changes are highly disease stage-specific, which has major implications for the study of neurodegenerative disorders.

Dataset Information

Gene expression profiling analysis of the putamen for the investigation of compensatory mechanisms in Parkinson's disease.

Publications

Gene expression profiling analysis of the putamen for the investigation of compensatory mechanisms in Parkinson's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets