Liliana Bernardino
Parkinson’s disease (PD), a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN), does not yet have an effective cure available. MicroRNA-124 (miR-124) has been regarded as a novel therapeutic entity for PD due to its pro-neurogenic and neuroprotective roles. However, its efficient delivery to the brain remains challenging. Previously, we have developed polymeric nanoparticles to deliver miR-124 in the brain. These miR-124-loaded nanoparticles were able to boost subventricular zone (SVZ) neurogenesis in vitro and in vivo and, ultimately, ameliorated motor deficits in a PD mouse model. Here, we used umbilical cord blood mononuclear cell-derived small extracellular vesicles as a biological vehicle to deliver miR-124 (miR-124 sEVs) to the brain, and its therapeutic effects were then evaluated in a 6-hydroxydopamine (6-OHDA) mouse model of PD. In vitro, miR-124 sEVs induced neurogenesis in SVZ neural stem cell cultures and protected N27 cells against 6-OHDA-induced toxicity. In vivo, intracerebroventricularly administered sEVs were found in the SVZ lining the lateral ventricles, striatum, and SN, the brain regions most affected by PD.