RT Journal Article
T1 Insulin-like growth factor II prevents oxidative and neuronal damage in cellular and mice models of Parkinson's disease.
A1 Martín-Montañez, Elisa
A1 Valverde, Nadia
A1 Ladrón de Guevara-Miranda, David
A1 Lara, Estrella
A1 Romero-Zerbo, Silvana Yanina
A1 Millón-Peñuela, Carmelo
A1 Boraldi, Federica
A1 Ávila-Gámiz, Fabiola
A1 Pérez-Cano, Ana María
A1 Garrido-Gil, Pablo
A1 Labandeira-García, José Luis
A1 Santín-Núñez, Luis Javier
A1 Pavía-Molina, José
A1 García-Fernández, María Inmaculada
K1 Parkinson, Enfermedad de
K1 Estrés oxidativo
K1 Somatomedina
K1 Sistema nervioso - Degeneración - Prevención
AB 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.
PB Elsevier
YR 2021
FD 2021
LK https://hdl.handle.net/10630/40705
UL https://hdl.handle.net/10630/40705
LA eng
NO Redox Biol. 2021 Oct;46:102095
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026