MicroRNA-124-3p-enriched small extracellular vesicles as a therapeutic approach for Parkinson's disease.

Autor:	Esteves M; Health Sciences Research Centre (CICS-UBI), Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal., Abreu R; Department of Molecular Genetics, Faculty of Sciences and Engineering, Maastricht University, Maastricht 6200, the Netherlands; CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC, Biotech Parque Tecnológico de Cantanhede, 3060-197 Cantanhede, Portugal., Fernandes H; CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC, Biotech Parque Tecnológico de Cantanhede, 3060-197 Cantanhede, Portugal; Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal., Serra-Almeida C; Health Sciences Research Centre (CICS-UBI), Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal., Martins PAT; CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC, Biotech Parque Tecnológico de Cantanhede, 3060-197 Cantanhede, Portugal., Barão M; CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC, Biotech Parque Tecnológico de Cantanhede, 3060-197 Cantanhede, Portugal., Cristóvão AC; Health Sciences Research Centre (CICS-UBI), Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal; Neurosov, UBImedical, EM506, University of Beira Interior, Covilhã, Portugal., Saraiva C; Health Sciences Research Centre (CICS-UBI), Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal., Ferreira R; Health Sciences Research Centre (CICS-UBI), Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal., Ferreira L; CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC, Biotech Parque Tecnológico de Cantanhede, 3060-197 Cantanhede, Portugal; Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal., Bernardino L; Health Sciences Research Centre (CICS-UBI), Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal. Electronic address: libernardino@fcsaude.ubi.pt.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2022 Oct 05; Vol. 30 (10), pp. 3176-3192. Date of Electronic Publication: 2022 Jun 09.
DOI:	10.1016/j.ymthe.2022.06.003
Abstrakt:	Parkinson's disease is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra with no effective cure available. MicroRNA-124 has been regarded as a promising therapeutic entity for Parkinson's disease due to its pro-neurogenic and neuroprotective roles. However, its efficient delivery to the brain remains challenging. Here, we used umbilical cord blood mononuclear cell-derived extracellular vesicles as a biological vehicle to deliver microRNA (miR)-124-3p and evaluate its therapeutic effects in a mouse model of Parkinson's disease. In vitro, miR-124-3p-loaded small extracellular vesicles induced neuronal differentiation in subventricular zone neural stem cell cultures and protected N27 dopaminergic cells against 6-hydroxydopamine-induced toxicity. In vivo, intracerebroventricularly administered small extracellular vesicles were detected in the subventricular zone lining the lateral ventricles and in the striatum and substantia nigra, the brain regions most affected by the disease. Most importantly, although miR-124-3p-loaded small extracellular vesicles did not increase the number of new neurons in the 6-hydroxydopamine-lesioned striatum, the formulation protected dopaminergic neurons in the substantia nigra and striatal fibers, which fully counteracted motor behavior symptoms. Our findings reveal a novel promising therapeutic application of small extracellular vesicles as delivery agents for miR-124-3p in the context of Parkinson's disease. Competing Interests: Declaration of interests The authors declare no conflict of interest. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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