RETRACTED ARTICLE: Gene expression profiling analysis of the putamen for the investigation of compensatory mechanisms in Parkinson’s disease

Huan Zhou,Honghua Gao,Lianbo Gao,Yanyuan Xu

doi:10.1186/1471-2377-13-181

Abstract

BackgroundParkinson’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.MethodsWe 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.ResultsTotal715 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.ConclusionIntrinsic striatal tyrosine hydroxylase interneurons growth may be promoted by changes in several genes expression and thus reduce the functional excitatory synapses.

Highlights

Parkinson’s disease (PD) is affecting 5 million people worldwide, but the response mechanisms of the striatum are still unclear
715 genes were screened between PD patients and normal controls with p-value < 0.05, including 268 up-regulated genes and 447 down-regulated genes
Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis GO functional enrichment analysis indicated that 715 differentially expressed genes (DEGs) were significantly enriched in 225 GO terms and the top 15 functional nodes were selected in which 5 functional nodes were related with neuron function, including neuron development, neuron differentiation, neuron projection development, neuron projection morphogenesis, and cell morphogenesis involved in neuron differentiation (Table 1)

Summary

Introduction

Parkinson’s disease (PD) is affecting 5 million people worldwide, but the response mechanisms of the striatum are still unclear. Depletion of dopaminergic nigrostriatal output leads to enhanced D2 receptors expression level in the striatum, which promotes the inhibitory effect of the rest dopamine in the striatum on the activity of the indirect pathway and delay manifestations of PD motor symptoms [9]. Activation of peroxisome proliferator–activated receptor γ coactivator1α (PGC-1α) may result in increased expression of nuclear-encoded subunits of the mitochondrial respiratory chain in the putamen of PD patients with dyskinesias [11] and block of the dopaminergic neuron loss caused by mutant α-synuclein or the pesticide rotenone [12]. The compensatory or response mechanisms in the putamen of PD patients are not very clear and underlying therapeutic targets are still needed to be investigated

Objectives

Methods

Results

Discussion

Conclusion