MiR-184 Mediated the Expression of ZNF865 in Exosome to Promote Procession in the PD Model

Abstract

AbstractExosomes are nanoscale small vesicles (EVs) secreted by cells that carry important bio information, including proteins, miRNAs, and more. Exosome contents are readily present in body fluids, including blood, and urine of humans and animals, and thereby act as markers of diseases. In patients with Parkinson’s disease (PD), exosomes may spread alpha-synuclein and miR-184 between the cells contributing to dopaminergic neuronal loss. In this study, we detected the levels of miR-184 in urine-excreted neuronal exosomes between PD patients and age-matched healthy subjects by qRT-PCR analysis. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were also used to determine the ultracellular structures of exosomes nanoparticles. MPP + and MPTP were used to construct the cell and animal PD model. Behavioral tests were used to detect motor performance. Furthermore, the cytological experiments were measured to examine the relationship between miR-184 and ZNF865. We found that the levels of miR-184 in urine-derived neuronal exosomes from PD patients were higher, compared to aged-matched normal people. The exosomes from PD patients were larger with greater numbers than those from the age-matched healthy subjects. The difference in miR-184 in urinary exosomes between PD patients and normal people may provide a novel perspective for early diagnosis of PD. However, no difference in CD63 level was observed in Exo-control and Exo-PD groups (exosome from control or PD groups). Moreover, ZNF865 was detected as the targeted gene of miR-184. In addition, miR-184 ASO (miR-184 antisense oligodeoxynucleotide, miR-184 ASO) could rescue the damage of neuronal apoptosis and motor performance in PD mice. Our results showed the miR-184 potential to function as a diagnostic marker of PD. Graphical Abstract