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MicroRNA-124-3p Modulates Alpha-Synuclein Expression Levels in a Paraquat-Induced in vivo Model for Parkinson’s Disease

2024-07Artigo científico Acesso aberto
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dc.contributor.authorEsteves, Marta
dc.contributor.authorCristóvão, Ana Clara
dc.contributor.authorVale, Ana
dc.contributor.authorMachado-Pereira, Marta
dc.contributor.authorFerreira, Raquel
dc.contributor.authorBernardino, Liliana
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblSpringer Science Business Media
dc.date.accessioned2024-03-26T23:53:58Z
dc.date.available2024-03-26T23:53:58Z
dc.date.issued2024-07
dc.descriptionFunding Information: Open access funding provided by FCT|FCCN (b-on). This work was partially supported by the Portuguese “Programa Operacional Regional do Centro, CENTRO 2020“ through the funding of ICON project (Interdisciplinary Challenges On Neurodegeneration; CENTRO-01-0145-FEDER-000013), and by the “Fundação para a Ciência e a Tecnologia (FCT)” under doctoral grant SFRH/BD/121822/2016. Publisher Copyright: © The Author(s) 2024.
dc.description.abstractParkinson’s disease (PD) is the second most prevalent neurodegenerative disease and the most common movement disorder. Although PD etiology is not fully understood, alpha (α)-synuclein is a key protein involved in PD pathology. MicroRNAs (miRNA), small gene regulatory RNAs that control gene expression, have been identified as biomarkers and potential therapeutic targets for brain diseases, including PD. In particular, miR-124 is downregulated in the plasma and brain samples of PD patients. Recently we showed that the brain delivery of miR-124 counteracts 6-hydroxydopamine-induced motor deficits. However, its role in α-synuclein pathology has never been addressed. Here we used paraquat (PQ)-induced rat PD model to evaluate the role of miR-124-3p in α-synuclein accumulation and dopaminergic neuroprotection. Our results showed that an intranigral administration of miR-124-3p reduced the expression and aggregation of α-synuclein in the substantia nigra (SN) of rats exposed to PQ. NADPH oxidases (NOX), responsible for reactive oxygen species generation, have been considered major players in the development of α-synuclein pathology. Accordingly, miR-124-3p decreased protein expression levels of NOX1 and its activator, small GTPase Rac1, in the SN of PQ-lesioned rats. Moreover, miR-124-3p was able to counteract the reduced levels of pituitary homeobox 3 (PITX3), a protein required for the dopaminergic phenotype, induced by PQ in the SN. This is the first study showing that miR-124-3p decreases PQ-induced α-synuclein levels and the associated NOX1/Rac1 signaling pathway, and impacts PITX3 protein levels, supporting the potential of miR-124-3p as a disease-modifying agent for PD and related α-synucleinopathies.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent1622528
dc.identifier.doi10.1007/s11064-024-04130-y
dc.identifier.issn0364-3190
dc.identifier.otherPURE: 85417218
dc.identifier.otherPURE UUID: f2c00ba7-09d0-415b-b4d1-b36dd534745e
dc.identifier.otherScopus: 85186923634
dc.identifier.urihttp://hdl.handle.net/10362/165484
dc.identifier.urlhttps://www.scopus.com/pages/publications/85186923634
dc.language.isoeng
dc.peerreviewedyes
dc.subjectAlpha-synuclein
dc.subjectmiR-124
dc.subjectParaquat
dc.subjectParkinson’s Disease
dc.subjectBiochemistry
dc.subjectCellular and Molecular Neuroscience
dc.titleMicroRNA-124-3p Modulates Alpha-Synuclein Expression Levels in a Paraquat-Induced in vivo Model for Parkinson’s Diseaseen
dc.typejournal article
degois.publication.firstPage1677
degois.publication.issue7
degois.publication.lastPage1686
degois.publication.titleNeurochemical Research
degois.publication.volume49
dspace.entity.typePublication
rcaap.rightsopenAccess

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