MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease

Abstract

Modulation of the subventricular zone (SVZ) neurogenic niche can enhance brain repair in several disorders including Parkinson's disease (PD). Herein, we used biocompatible and traceable polymeric nanoparticles (NPs) containing perfluoro-1,5-crown ether (PFCE) and coated with protamine sulfate to complex microRNA-124 (miR-124), a neuronal fate determinant. The ability of NPs to efficiently deliver miR-124 and prompt SVZ neurogenesis and brain repair in PD was evaluated. In vitro, miR-124 NPs were efficiently internalized by neural stem/progenitors cells and neuroblasts and promoted their neuronal commitment and maturation. The expression of Sox9 and Jagged1, two miR-124 targets and stemness-related genes, were also decreased upon miR-124 NP treatment. In vivo, the intracerebral administration of miR-124 NPs increased the number of migrating neuroblasts that reached the granule cell layer of the olfactory bulb, both in healthy and in a 6-hydroxydopamine (6-OHDA) mouse model for PD.MiR-124 NPs were also able to induce migration of neurons into the lesioned striatum of 6-OHDA-treated mice. Most importantly, miR-124 NPs proved to ameliorate motor symptoms of 6-OHDA mice, monitored by the apomorphine-induced rotation test.Altogether, we provide clear evidences to support the use of miR-124 NPs as a new therapeutic approach to boost endogenous brain repair mechanisms in a setting of neurodegeneration.

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

“…A strong relationship between miRNA and pathophysiological processes has been reported in the literature [20,21]. As mentioned in the literature review, miR-124 is frequently expressed in multiple tissues to regulate different pathophysiologic processes, for instance, the development of cancer [22][23][24][25][26], as a new therapeutic approach to Parkinson's disease [27], promotes the pathogenesis of Crohn's Disease [28] and contributes to cholangiocyte proliferation in the cholestatic liver [29].…”

Long non-coding RNA MALAT1 contributes to cell apoptosis by sponging miR-124 in Parkinson disease

“…It has been estimated that approximately 8–18 new diagnosed PD cases will appear per 1,010,000 persons per year [2]. PD is characterized by the specific loss of dopaminergic (DA) neurons presented in the substantia nigra pars compacta (SNpc) along with widespread intracellular α-synuclein (α-syn) aggregates in several mammalian species, which triggered aberrant nerve signal that leads to movement coordination impairment and cognitive deficits [3]. Current treatments available for PD relieve the symptom instead of inhibiting the development of PD.…”

Non‐viral nucleic acid delivery to the central nervous system and brain tumors

“…Other important miRNAs, including miRNA‐133b, miRNA‐124 and miRNA‐155 were found to be significantly deficient in PD brain tissues, which could disrupt normal brain functions. Saraiva et al . prepared miRNA‐124‐loaded nanoparticles and evaluated their therapeutic potential for a 6‐hydroxydopamine‐lesioned PD mice model.…”