RT Conference Proceedings
T1 Insulin-like growth factor II neuroprotective effects against mitochondrial-oxidative and neuronal damage induced by CORT and MPP+ in dopaminergic neurons
A1 Claros-Gil, Silvia
A1 Cabrera García, Pablo
A1 Valverde, Nadia
A1 Romero-Zerbo, Silvana Yanina
A1 Lara, Estrella
A1 López-González, Manuel Víctor
A1 Shumilov, Kirill
A1 Rivera-Ramírez, Alicia
A1 Pavía-Molina, José
A1 Martín-Montañez, Elisa
A1 García-Fernández, María Inmaculada
K1 Insulina
K1 Parkinson, Enfermedad de
AB Aims: Parkinson’s disease (PD) affects 1–3% of the population aged over 65. Stress seems to contribute toPD neuropathology, probably by dysregulation of the hypothalamic–pituitary–adrenal axis. Key factors areoxidative stress, mitochondrial dysfunction and neuronal glucocorticoid-induced toxicity. Insulin-like growthfactor 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 combinedmodel of PD and mild to moderate stress, based on corticosterone (CORT) and the dopaminergicneurotoxin 1-methyl-4-phenylpyridinium (MPP+).Methods: The dopaminergic neuronal cell line SN4741 (RRID:CVCL_S466) derived from mouse substantianigra 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 signalingpathways were evaluated.Results: The administration of MPP+ or CORT individually led to cell damage compared to controlsituations, whereas the combination of both drugs produced very considerable toxic synergistic effect. IGF-IIcounteracts the mitochondrial-oxidative damage, protecting dopaminergic neurons from death andneurodegeneration. IGF-II promotes PKC activation and nuclear factor (erythroid-derived 2)-like 2antioxidant response in a glucocorticoid receptor-dependent pathway, preventing oxidative cell damageand maintaining mitochondrial function.Conclusions: IGF-II capacity to protect nigral dopamine neurons against mitochondrial-oxidative damageinduced by CORT and MPP+ was demonstrated. Thus, IGF-II is a potential therapeutic tool for preventionand treatment of PD patients suffering mild to moderate emotional stress.
YR 2022
FD 2022-07-12
LK https://hdl.handle.net/10630/24735
UL https://hdl.handle.net/10630/24735
LA eng
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026