2026-05-27T05:32:41Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/247352026-02-03T12:32:09Zcom_10630_2254col_10630_37959

Insulin-like growth factor II neuroprotective effects against mitochondrial-oxidative and neuronal damage induced by CORT and MPP+ in dopaminergic neurons Claros-Gil, Silvia Cabrera García, Pablo Valverde, Nadia Romero-Zerbo, Silvana Yanina Lara, Estrella López-González, Manuel Víctor Shumilov, Kirill Rivera-Ramírez, Alicia Pavía-Molina, José Martín-Montañez, Elisa García-Fernández, María Inmaculada Insulina Parkinson, Enfermedad de Aims: Parkinson’s disease (PD) affects 1–3% of the population aged over 65. Stress seems to contribute to PD neuropathology, probably by dysregulation of the hypothalamic–pituitary–adrenal axis. Key factors are oxidative stress, mitochondrial dysfunction and neuronal glucocorticoid-induced toxicity. Insulin-like growth factor II (IGF-II) has shown antioxidant and neuroprotective effects in some neurodegenerative disorders. Therefore, our aim was to study IGF-II protective effects against oxidative damage on a cellular combined model of PD and mild to moderate stress, based on corticosterone (CORT) and the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Methods: The dopaminergic neuronal cell line SN4741 (RRID:CVCL_S466) derived from mouse substantia nigra were exposed to 200 μM MPP+, 0.5 μM CORT or both, with or without 25 ng/mL IGF-II, for 2.5 or 6 h. Cell viability, oxidative stress parameters, mitochondrial and dopamine markers and intracellular signaling pathways were evaluated. Results: The administration of MPP+ or CORT individually led to cell damage compared to control situations, whereas the combination of both drugs produced very considerable toxic synergistic effect. IGF-II counteracts the mitochondrial-oxidative damage, protecting dopaminergic neurons from death and neurodegeneration. IGF-II promotes PKC activation and nuclear factor (erythroid-derived 2)-like 2 antioxidant response in a glucocorticoid receptor-dependent pathway, preventing oxidative cell damage and maintaining mitochondrial function. Conclusions: IGF-II capacity to protect nigral dopamine neurons against mitochondrial-oxidative damage induced by CORT and MPP+ was demonstrated. Thus, IGF-II is a potential therapeutic tool for prevention and treatment of PD patients suffering mild to moderate emotional stress. 2022-07-20T06:26:53Z 2022-07-20T06:26:53Z 2022 2022-07-12 conference output https://hdl.handle.net/10630/24735 eng FENS Forum 2022 París 09/07/2022 open access