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dc.contributor.author | Martín-Montañez, Elisa | |
dc.contributor.author | Valverde, Nadia | |
dc.contributor.author | Ladrón de Guevara-Miranda, David | |
dc.contributor.author | Lara, Estrella | |
dc.contributor.author | Romero-Zerbo, Yanina S. | |
dc.contributor.author | Millon, Carmelo | |
dc.contributor.author | Boraldi, Federica | |
dc.contributor.author | Ávila-Gámiz, Fabiola | |
dc.contributor.author | Pérez-Cano, Ana M. | |
dc.contributor.author | Garrido-Gil, Pablo | |
dc.contributor.author | Labandeira-Garcia, Jose Luis | |
dc.contributor.author | Santin, Luis J. | |
dc.contributor.author | Pavia, Jose | |
dc.contributor.author | Garcia-Fernandez, Maria | |
dc.date.accessioned | 2024-02-19T15:30:25Z | |
dc.date.available | 2024-02-19T15:30:25Z | |
dc.date.issued | 2021-08 | |
dc.identifier.other | http://hdl.handle.net/10668/4269 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/18423 | |
dc.description.abstract | Oxidative distress and mitochondrial dysfunction, are key factors involved in the pathophysiology of Parkinson's disease (PD). The pleiotropic hormone insulin-like growth factor II (IGF-II) has shown neuroprotective and antioxidant effects in some neurodegenerative diseases. In this work, we demonstrate the protective effect of IGF-II against the damage induced by 1-methyl-4-phenylpyridinium (MPP+) in neuronal dopaminergic cell cultures and a mouse model of progressive PD. In the neuronal model, IGF-II counteracts the oxidative distress produced by MPP + protecting dopaminergic neurons. Improved mitochondrial function, increased nuclear factor (erythroid-derived 2)-like2 (NRF2) nuclear translocation along with NRF2-dependent upregulation of antioxidative enzymes, and modulation of mammalian target of rapamycin (mTOR) signalling pathway were identified as mechanisms leading to neuroprotection and the survival of dopaminergic cells. The neuroprotective effect of IGF-II against MPP + -neurotoxicity on dopaminergic neurons depends on the specific IGF-II receptor (IGF-IIr). In the mouse model, IGF-II prevents behavioural dysfunction and dopaminergic nigrostriatal pathway degeneration and mitigates neuroinflammation induced by MPP+. Our work demonstrates that hampering oxidative stress and normalising mitochondrial function through the interaction of IGF-II with its specific IGF-IIr are neuroprotective in both neuronal and mouse models. Thus, the modulation of the IGF-II/IGF-IIr signalling pathway may be a useful therapeutic approach for the prevention and treatment of PD. | |
dc.description.sponsorship | This research was supported by the following projects: M.G-F.& L.J.S. Proyectos I+D+I-Programa Operativo FEDER Andalucía 2014–2020 (UMA18-FEDERJA- 004) Junta de Andalucía that also partially supported N. Valverde; CTS507 and CTS156 from Consejería de Economía Innovación Ciencia y Empresa, Junta de Andalucía; and Fondo Social Europeo (EU) supported partially N. Valverde. L.J.S.: Ministerio de Economía y Competitividad. Gobierno de España. (MINECO, Agencia Estatal de Investigación cofinanciado por FEDER -UE. (PSI2017-82604R). | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Insulin like growth factor-II | |
dc.subject | Neuroprotection | |
dc.subject | Mitochondria | |
dc.subject | Oxidative distress | |
dc.subject | Parkinson’s disease | |
dc.subject | 1-methyl-4-phenylpyridinium | |
dc.subject | Dopaminergic neurons | |
dc.subject | Factor II del crecimiento similar a la insulina | |
dc.subject | Neuroprotección | |
dc.subject | Mitocondrias | |
dc.subject | Estrés oxidativo | |
dc.subject | Enfermedad de Parkinson | |
dc.subject | 1-metil-4-fenilpiridinio | |
dc.subject | Neuronas dopaminérgicas | |
dc.subject.mesh | 1-Methyl-4-phenylpyridinium | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Dopaminergic Neurons | |
dc.subject.mesh | Insulin-Like Growth Factor II | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Oxidative Stress | |
dc.subject.mesh | Parkinson Disease | |
dc.subject.mesh | Neuroprotective Agents | |
dc.subject.mesh | NF-E2-Related Factor 2 | |
dc.subject.mesh | Antioxidants | |
dc.subject.mesh | Receptor, IGF Type 2 | |
dc.subject.mesh | Neurodegenerative Diseases | |
dc.subject.mesh | Up-Regulation | |
dc.subject.mesh | Mitochondria | |
dc.subject.mesh | TOR Serine-Threonine Kinases | |
dc.subject.mesh | Cell Culture Techniques | |
dc.subject.mesh | Hormones | |
dc.title | Insulin-like growth factor II prevents oxidative and neuronal damage in cellular and mice models of Parkinson's disease | |
dc.type | research article | |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 International | * |
dc.identifier.pubmedID | 34418603 | es_ES |
dc.identifier.doi | 10.1016/j.redox.2021.102095 | |
dc.identifier.e-issn | 2213-2317 | es_ES |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S2213231721002548?via%3Dihub | es |
dc.identifier.journal | Redox Biology | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.contributor.authoraffiliation | [Martín-Montañez,E; Valverde,N; Pavia,J] Departamento de Farmacología y Pediatría, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Málaga, Spain. [Ladrón de Guevara-Miranda,D; Ávila-Gámiz,F; Pérez-Cano,AM; Santin,LJ] Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Málaga, Spain. [Valverde,N; Lara,E; Romero-Zerbo,YS; Millon,C; Garcia-Fernandez,M] Departamento de Fisiología Humana, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Málaga, Spain. [Boraldi,F] Dipartimento di Scienze della Vita. Patologia Generale.Universita di Modena e Reggio Emilia, Italy. [Garrido-Gil,P; Labandeira-Garcia,JL] Centro de Investigación en Medicina Molecular y Enfermedades Crónicas (CiMUS) y Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED-Madrid). Universidad de Santiago de Compostela, Spain. |
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