Integrated Analysis and Identification of Novel Biomarkers in Parkinson’s Disease

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.

Protein Deimination Signatures in Plasma and Plasma-EVs and Protein Deimination in the Brain Vasculature in a Rat Model of Pre-Motor Parkinson’s Disease

“…Interestingly, a link via mitochondrial dysfunction has been made between metabolic syndrome, diabetes, obesity, and non-alcoholic fatty liver disease in the progression of AD, PD, and other neurodegenerative diseases [108]. Furthermore, lipid metabolism (in particular non-alcoholic fatty liver disease pathway) and mitochondrial dysregulation have been identified as molecular pathways and putative biomarkers linked to PD [109]. Post-translational deimination is revealed for the first time for NAFLD associated KEGG pathways in this study and may be of relevance for the interplay of neurodegeneration and such comorbidities.…”

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases

“…PAK (p21 activated kinase) is a family of serine/threonine kinases that function as Rac and Cdc42 GTPases effector molecules, and they are implicated in the signal transduction emanating from integrins and tyrosine kinase receptors. Furthermore, PAK has been related to neurodegenerative diseases [ 93 ]. In a healthy brain, PAK is involved in the regulation of neuron viability, synapse morphology and functionality, gene transcription in neurons, microglial motility, microglial immune response, and astrogliosis [ 94 ].…”

“…It has been demonstrated using post-mortem brain samples that Cdc42 expression is elevated in the prefrontal cortex of AD patients [ 104 ]. Gene expression database analyses have shown that PD patients have reduced Cdc42 mRNA levels [ 93 ]. Together, this data indicates that Cdc42 could play an important role in neurodegeneration.…”

Differential gene expression in the interactome of the Human Dopamine transporter in the context of Parkinson’s disease

“…Regarding the to miRNA – target interactions (MTIs) in interatome hDAT and are deregulated in PD, in a previous study of Parkinson’s patients that aimed to the Identification of Novel Biomarkers in PD was carried out as follows approach: i)experimentally supported databases with experimentally verified and ii) different prediction algorithms[13], which allows obtaining the following resulted miRNAs : miR-126-5p, hsa-miR-29b-3p, and hsa-miR-301a-3p which are also described in the present study about this miRNAs and interaction with mRNA previously described that miR-126-5p interaction with CAMK2A [53], EPS15 [53, 54], NEDD4 and SNCA[56], the hsa-miR-29b-3p interaction with EPS15 [57], CDH1 [58], GPR37[59] and the hsa-miR-301a-3p interaction with CSK[60] and EPS15[61] which are also part of hDAT interactome, which although we found miRNAs that interacted with multiple mRNAs of hDAT interactome proteins, which presented altered expression in PD vs controls, we did not find any type of relationship either in the number of miRNAs per target of the interactome, or in the combined estimate of rate of miRNA change and the combined estimate of rate of change in hDAT interactome mRNAs.…”