miRNAs and target genes in the blood as biomarkers for the early diagnosis of Parkinson’s disease

Abstract

BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disease, and it is a multifactorial disease with no definite diagnostic index. The aim of this study is to construct a molecular network to find molecules that play important roles in the progression of PD with the goal of using them diagnostically and for early intervention.ResultsWe downloaded two gene expression profiles (GSE54536 and GSE100054) from the Expression Omnibus (GEO) database to analyze possible markers. The Genes were analyzed with GEO2R. There were 1790 and 967 differentially expressed genes (DEGs) in GSE54536 and GSE100054 respectively. A total of 125 genes co-exist in the DEGs of the two data sets. KEGG pathway analysis showed that 125 DEGs were enriched in Aldosterone synthesis and secretion, Gap junctions, Platelet activation, Rap1 signaling pathway, and Estrogen signaling pathway. There were 20 hub genes among 125 DEGs analyzed by PPI that involved in Platelet activation, Inflammatory response, Innate immune response, B cell receptor signaling, Stimulatory C-type lectin receptor signaling, Lipopolysaccharide response, Leukocyte migration, and Regulation of cell proliferation. Additionally, 42 differences in miRNAs were found in GSE100054. We constructed a miRNA-mRNA regulatory network depicting interactions between the predicted genes and the 125 DEGs. 34 miRNA-mRNA pairs were obtained. We found GNAQ and TMTC2 were the most important mRNAs in the network analyzed by Cytoscape APP centiscape, and their degrees in centiscape2.2 were all 10. has-miR-142 was the most important miRNA (the highest degree is 4 in centiscape2.2), which forms miRNA-mRNA pairs with GNAQ, TMTC2, BEND2, and KYNU.ConclusionsThis study provides data of potential biomarkers and therapeutic targets for PD diagnosis and treatment. Among them, hsa-miR-142 is a critical miRNA in the PD network, and may be involved in PD progression by regulating GNAQ, TMTC2, BEND2, and KYNU.

Deep sncRNA-seq of the PPMI cohort to study Parkinson’s disease progression

“…We also observed a systematic decline in miRNA expression over time, revealing a signature of miRNAs associated with leukocytes, in particular monocytes and B cells, as well as exosomes and RBCs. Among these are several members of the miR-19 and miR-29 families that are consistent with earlier findings [33][34][35][36][37] . Also, PD induced changes for both monocyte and exosome expression signatures has been reported in several other studies [38][39][40][41] .…”

“…Surprisingly, miRNA expression signatures distinguish between iPD and genetic PD, for which effects between disease and controls were largest for iPD. The observed down-regulation of miR-15b-5p is in line with a proposed signature of 5 serum miRNAs in PD patients 32 and a miRNA-mRNA interaction network analysis of PD progression 33 . We also observed a systematic decline in miRNA expression over time, revealing a signature of miRNAs associated with leukocytes, in particular monocytes and B cells, as well as exosomes and RBCs.…”

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

“…EV-cargo was assessed for deiminated proteins as well as for three key microRNAs known to contribute to inflammation and hypoxia (miR21, miR155, and miR210), all of which have also been associated to neurodegenerative diseases and PD [23][24][25], but have not been related to, or assessed in, pre-motor PD before the current study. Epigenetic mechanisms of PD have indeed received increasing attention, including histone modifications, DNA methylation, as well as microRNA involvement [26,27]. Our findings identify EVs and protein deimination as novel markers in pre-motor stages of PD.…”

“…Gap junction and platelet activation were identified in this study as KEGG pathways enriched in deiminated proteins in pre-motor PD plasma EVs. Reduced platelet activation has been described in PD [74] and furthermore a recent study has identified gap junctions and platelet activation as KEGG pathways in early PD [26]. Gap junctions are formed by pannexins and connexins and allow for exchange of ions, second messengers, and small metabolites between adjacent cells [75].…”

Precision Medicine in Neurodegenerative Diseases: Some Promising Tips Coming from the microRNAs’ World

“…Currently no clinically validated biomarkers for PD monitoring has been identified [62]. However, there are evidences that miRNAs can be associated with PD pathophysiology as well, since they seem to be involved in the disease progression by regulating different PD-related genes [14,[63][64][65].…”