2026-06-14T03:40:14Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/184232024-11-28T15:00:29Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
Martín-Montañez, Elisa
author
Valverde, Nadia
author
Ladrón de Guevara-Miranda, David
author
Lara, Estrella
author
Romero-Zerbo, Yanina S.
author
Millon, Carmelo
author
Boraldi, Federica
author
Ávila-Gámiz, Fabiola
author
Pérez-Cano, Ana M.
author
Garrido-Gil, Pablo
author
Labandeira-Garcia, Jose Luis
author
Santin, Luis J.
author
Pavia, Jose
author
Garcia-Fernandez, Maria
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.
2024-02-19T15:30:25Z
2024-02-19T15:30:25Z
2021-08
10.1016/j.redox.2021.102095
2213-2317
Redox Biology
http://hdl.handle.net/10668/4269
34418603
http://hdl.handle.net/20.500.12105/18423
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.
eng
Insulin like growth factor-II
Neuroprotection
Mitochondria
Oxidative distress
Parkinson’s disease
1-methyl-4-phenylpyridinium
Dopaminergic neurons
Factor II del crecimiento similar a la insulina
Neuroprotección
Mitocondrias
Estrés oxidativo
Enfermedad de Parkinson
1-metil-4-fenilpiridinio
Neuronas dopaminérgicas
Insulin-like growth factor II prevents oxidative and neuronal damage in cellular and mice models of Parkinson's disease
research article