Protein Binding Partners of Dysregulated miRNAs in Parkinson’s Disease Serum

Abstract

Accumulating evidence suggests that microRNAs (miRNAs) are a contributing factor to neurodegenerative diseases. Although altered miRNA profiles in serum or plasma have been reported for several neurodegenerative diseases, little is known about the interaction between dysregulated miRNAs and their protein binding partners. We found significant alterations of the miRNA abundance pattern in serum and in isolated serum-derived extracellular vesicles of Parkinson’s disease (PD) patients. The differential expression of miRNA in PD patients was more robust in serum than in isolated extracellular vesicles and could separate PD patients from healthy controls in an unsupervised approach to a high degree. We identified a novel protein interaction partner for the strongly dysregulated hsa-mir-4745-5p. Our study provides further evidence for the involvement of miRNAs and HNF4a in PD. The demonstration that miRNA-protein binding might mediate the pathologic effects of HNF4a both by direct binding to it and by binding to proteins regulated by it suggests a complex role for miRNAs in pathology beyond the dysregulation of transcription.