Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/18423
Title
Insulin-like growth factor II prevents oxidative and neuronal damage in cellular and mice models of Parkinson's disease
Author(s)
Martín-Montañez, Elisa | Valverde, Nadia | Ladrón de Guevara-Miranda, David | Lara, Estrella | Romero-Zerbo, Yanina S. | Millon, Carmelo | Boraldi, Federica | Ávila-Gámiz, Fabiola | Pérez-Cano, Ana M. | Garrido-Gil, Pablo | Labandeira-Garcia, Jose Luis | Santin, Luis J. | Pavia, Jose | Garcia-Fernandez, Maria
Date issued
2021-08
Language
Inglés
Document type
research article
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.
Subject
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
MESH
1-Methyl-4-phenylpyridinium | Animals | Dopaminergic Neurons | Insulin-Like Growth Factor II | Mice | Oxidative Stress | Parkinson Disease | Neuroprotective Agents | NF-E2-Related Factor 2 | Antioxidants | Receptor, IGF Type 2 | Neurodegenerative Diseases | Up-Regulation | Mitochondria | TOR Serine-Threonine Kinases | Cell Culture Techniques | Hormones
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