2026-06-14T03:44:44Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/184232024-11-28T15:00:29Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc 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 author 2021-08 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. 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 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