Martín-Montañez, ElisaValverde, NadiaLadrón de Guevara-Miranda, DavidLara, EstrellaRomero-Zerbo, Yanina S.Millon, CarmeloBoraldi, FedericaÁvila-Gámiz, FabiolaPérez-Cano, Ana M.Garrido-Gil, PabloLabandeira-Garcia, Jose LuisSantin, Luis J.Pavia, JoseGarcia-Fernandez, Maria2022-10-212022-10-212021-08Martín-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.http://hdl.handle.net/10668/4269Oxidative 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.enAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Insulin like growth factor-IINeuroprotectionMitochondriaOxidative distressParkinson’s disease1-methyl-4-phenylpyridiniumDopaminergic neuronsFactor II del crecimiento similar a la insulinaNeuroprotecciónMitocondriasEstrés oxidativoEnfermedad de Parkinson1-metil-4-fenilpiridinioNeuronas dopaminérgicasMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyridines::Pyridinium Compounds::1-Methyl-4-phenylpyridiniumMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Nervous System::Neurons::Dopaminergic NeuronsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Somatomedins::Insulin-Like Growth Factor IIMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative StressMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson DiseaseMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Protective Agents::Neuroprotective AgentsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Basic-Leucine Zipper Transcription Factors::NF-E2-Related Factor 2Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::AntioxidantsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Peptide::Receptors, Growth Factor::Receptors, Somatomedin::Receptor, IGF Type 2Medical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative DiseasesMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Up-RegulationMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::MitochondriaMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::TOR Serine-Threonine KinasesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Culture TechniquesMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormonesresearch article34418603Acceso abierto10.1016/j.redox.2021.1020952213-2317PMC8379511