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, Yanina S.
A1 Millon, Carmelo
A1 Boraldi, Federica
A1 Ávila-Gámiz, Fabiola
A1 Pérez-Cano, Ana M.
A1 Garrido-Gil, Pablo
A1 Labandeira-Garcia, Jose Luis
A1 Santin, Luis J.
A1 Pavia, Jose
A1 Garcia-Fernandez, Maria
K1 Insulin like growth factor-II
K1 Neuroprotection
K1 Mitochondria
K1 Oxidative distress
K1 Parkinson’s disease
K1 1-methyl-4-phenylpyridinium
K1 Dopaminergic neurons
K1 Factor II del crecimiento similar a la insulina
K1 Neuroprotección
K1 Mitocondrias
K1 Estrés oxidativo
K1 Enfermedad de Parkinson
K1 1-metil-4-fenilpiridinio
K1 Neuronas dopaminérgicas
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 B.V.
YR 2021
FD 2021-08
LK http://hdl.handle.net/10668/4269
UL http://hdl.handle.net/10668/4269
LA en
NO Martín-Montañez E, Valverde N, Ladrón de Guevara-Miranda D, Lara E, Romero-Zerbo YS, Millon C, et al. Insulin-like growth factor II prevents oxidative and neuronal damage in cellular and mice models of Parkinson's disease. Redox Biol. 2021 Oct;46:102095.
DS RISalud
RD Apr 8, 2025