Traceable microRNA-124 loaded nanoparticles as a new promising therapeutic tool for Parkinson's disease.

Parkinson's disease (PD), a neurodegenerative disorder characterized by the selective degeneration of the nigrostriatal dopaminergic pathway, is a major socio-economic burden in modern society. While there is presently no cure for PD, enhancing the number of neural stem cells (NSCs) and/or stimulating their differentiation into new neurons are promising therapeutic strategies. Many proneurogenic factors have been implicated in controlling NSCs activity, including the microRNA (miR)-124. However, current strategies described for the intracellular delivery of miR involve mostly unspecific or inefficient platforms. In Saraiva et al. we developed miR-124 loaded nanoparticles (NPs) able to efficiently deliver miR-124 into neural stem/progenitor cells and boost neuronal differentiation and maturation in vitro. In vivo, the intracerebroventricular injection of miR-124 NPs increased the number of new neurons in the olfactory bulb of healthy and 6-hydroxidopamine (6-OHDA) lesioned mice, a model for PD. Importantly, miR-124 NPs enhanced the migration of new neurons into the 6-OHDA lesioned striatum, culminating in motor function improvement. Given the recent advent of clinical trials for miR-based therapies and the theranostic applications of our NPs, we expect to support the clinical translation of our delivery platform in the context of PD and other neurodegenerative diseases which may benefit from enhancing miR levels.