Abstract
Parkinson’s disease (PD) is a quite common neurodegenerative disorder with a prevalence of approximately 1:800–1,000 in subjects over 60 years old. The aim of our study was to determine the candidate target genes in PD through meta-analysis of multiple gene expression arrays datasets and to further combine mRNA and miRNA expression analyses to identify more convincing biological targets and their regulatory factors. Six included datasets were obtained from the Gene Expression Omnibus database by systematical search, including five mRNA datasets (150 substantia nigra samples in total) and one miRNA dataset containing 32 peripheral blood samples. A chip meta-analysis of five microarray data was conducted by using the metaDE package and 94 differentially expressed (DE) mRNAs were comprehensively obtained. And 19 deregulated DE miRNAs were obtained through the analysis of one miRNAs dataset by Qlucore Omics Explorer software. An interaction network formed by DE mRNAs, DE miRNAs, and important pathways was discovered after we analyzed the functional enrichment, protein–protein interactions, and miRNA targetome prediction analysis. In conclusion, this study suggested that five significantly downregulated mRNAs (MAPK8, CDC42, NDUFS1, COX4I1, and SDHC) and three significantly downregulated miRNAs (miR-126-5p, miR-19-3p, and miR-29a-3p) were potentially useful diagnostic markers in clinic, and lipid metabolism (especially non-alcoholic fatty liver disease pathway) and mitochondrial dysregulation may be the keys to biochemically detectable molecular defects. However, the role of these new biomarkers and molecular mechanisms in PD requires further experiments in vivo and in vitro and further clinical evidence.
Highlights
Parkinson’s disease (PD) is a quite common neurodegenerative disorder with a prevalence of approximately 1:800–1,000 in subjects over 60 years of age (Bekris et al, 2010; Lin and Farrer, 2014)
Six primary datasets with available mRNA expression data for substantia nigra (SN) samples in PD patients and controls were identified by searching the Gene Expression Omnibus (GEO) database (GSE20186, GSE8397, GSE20141, GSE20333, GSE7621, and GSE20295)
We identified 94 mRNAs showing consistent differentially expressed (DE) patterns using a penalized t-test by adding a fudging parameter, and the maximum P-value and Fisher’s method by summarizing −log (P-value) across studies were chosen to eliminate the significant influence of the large number of samples (Lu et al, 2010)
Summary
Parkinson’s disease (PD) is a quite common neurodegenerative disorder with a prevalence of approximately 1:800–1,000 in subjects over 60 years of age (Bekris et al, 2010; Lin and Farrer, 2014). Several genes have been shown to be closely related to PD, such as α-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2), Parkin RBRE3 ubiquitin protein ligase (PRKN), Parkinsonism associated deglycase (PARK7), PTEN-induced putative kinase 1 (PINK1), and ATPase 13A2 (ATP13A2) (Bekris et al, 2010; Nuytemans et al, 2010; Klein and Westenberger, 2012; Heman-Ackah et al, 2013) Because these mutations do not cause disease directly, it is more likely that they make people more susceptible to the PD when in cooperation with other risk factors (Lesage and Brice, 2009). The exploration of PD has been explored for nearly a century, the pathogenesis of PD is not yet clear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
