Cell-free microRNAs in Parkinson's disease: potential biomarkers that provide new insights into disease pathogenesis

MicroRNAs (miRNAs) are master post-transcriptional regulators of gene expression and their specific footprints reflect disease conditions. Over the last few years, several primary reports have described the deregulation of cell-free miRNAs in Parkinson's disease (PD), however, results have been rather inconsistent due to preanalytical and analytical challenges. This study integrated the data across twenty-four reports to identify steadily de-regulated miRNAs that may assist in the path towards biomarker development and molecular characterization of the underlying pathology. Stringent KEGG pathway analysis of the miRNA targets revealed FoxO, Prolactin, TNF, and ErbB signaling pathways as the most significantly enriched categories while Gene Ontology analysis revealed that the protein targets are mostly associated with transcription. Chromosomal location of the consistently deregulated miRNAs revealed that over a third of them were clustered at the same location at Chr14q32 suggesting that they are co-regulated by specific transcription factors. This genomic region is inherently unstable due to expanded TGG repeats and responsible for human abnormalities. Stringent analysis of transcription factor sites surrounding the deregulated miRNAs revealed that CREB1, CEBPB and MAZ sites existed in approximately half of the miRNAs, including all of the miRNAs located at Chr14q32. Additional studies are now needed to determine the biomarker potential of the consistently deregulated miRNAs in PD and the therapeutic implications of these bioinformatics insights.