New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson’s disease
Introduction: One of the hallmarks of Parkinsońs Disease (PD) is oxidative distress, leading to mitochondrial dysfunction and neurodegeneration. Insulin-like growth factor II (IGF-II) has been proven to have antioxidant and neuroprotective effects in some neurodegenerative diseases, including PD. C...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224000493 |
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| author | Silvana-Yanina Romero-Zerbo Nadia Valverde Silvia Claros Pablo Zamorano-Gonzalez Federica Boraldi Francesco-Demetrio Lofaro Estrella Lara Jose Pavia Maria Garcia-Fernandez Belen Gago Elisa Martin-Montañez |
| author_facet | Silvana-Yanina Romero-Zerbo Nadia Valverde Silvia Claros Pablo Zamorano-Gonzalez Federica Boraldi Francesco-Demetrio Lofaro Estrella Lara Jose Pavia Maria Garcia-Fernandez Belen Gago Elisa Martin-Montañez |
| author_sort | Silvana-Yanina Romero-Zerbo |
| collection | DOAJ |
| description | Introduction: One of the hallmarks of Parkinsońs Disease (PD) is oxidative distress, leading to mitochondrial dysfunction and neurodegeneration. Insulin-like growth factor II (IGF-II) has been proven to have antioxidant and neuroprotective effects in some neurodegenerative diseases, including PD. Consequently, there is growing interest in understanding the different mechanisms involved in the neuroprotective effect of this hormone. Objectives: To clarify the mechanism of action of IGF-II involved in the protective effect of this hormone. Methods: The present study was carried out on a cellular model PD based on the incubation of dopaminergic cells (SN4741) in a culture with the toxic 1-methyl-4-phenylpyridinium (MPP+), in the presence of IGF-II. This model undertakes proteomic analyses in order to understand which molecular cell pathways might be involved in the neuroprotective effect of IGF-II. The most important proteins found in the proteomic study were tested by Western blot, colorimetric enzymatic activity assay and immunocytochemistry. Along with the proteomic study, mitochondrial morphology and function were also studied by transmission electron microscopy and oxygen consumption rate. The cell cycle was also analysed using 7AAd/BrdU staining, and flow cytometry. Results: The results obtained indicate that MPP+, MPP++IGF-II treatment and IGF-II, when compared to control, modified the expression of 197, 246 proteins and 207 respectively. Some of these proteins were found to be involved in mitochondrial structure and function, and cell cycle regulation. Including IGF-II in the incubation medium prevents the cell damage induced by MPP+, recovering mitochondrial function and cell cycle dysregulation, and thereby decreasing apoptosis. Conclusion: IGF-II improves mitochondrial dynamics by promoting the association of Mitofilin with mitochondria, regaining function and redox homeostasis. It also rebalances the cell cycle, reducing the amount of apoptosis and cell death by the regulation of transcription factors, such as Checkpoint kinase 1. |
| format | Article |
| id | doaj-art-89295d7773eb42de93c1dfb655777c9f |
| institution | Kabale University |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Journal of Advanced Research |
| spelling | doaj-art-89295d7773eb42de93c1dfb655777c9f2024-12-18T08:48:11ZengElsevierJournal of Advanced Research2090-12322025-01-0167349359New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson’s diseaseSilvana-Yanina Romero-Zerbo0Nadia Valverde1Silvia Claros2Pablo Zamorano-Gonzalez3Federica Boraldi4Francesco-Demetrio Lofaro5Estrella Lara6Jose Pavia7Maria Garcia-Fernandez8Belen Gago9Elisa Martin-Montañez10Departamento de Fisiología Humana, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Malaga 29010, SpainDepartamento de Farmacología y Pediatría, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Malaga 29010, SpainDepartamento de Fisiología Humana, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Malaga 29010, SpainDepartamento de Fisiología Humana, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Malaga 29010, SpainDipartimento di Scienze Della Vita. Patologia Generale, Universita di Modena e Reggio Emilia 4112, ItalyDipartimento di Scienze Della Vita. Patologia Generale, Universita di Modena e Reggio Emilia 4112, ItalyDepartamento de Fisiología Humana, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Malaga 29010, SpainDepartamento de Farmacología y Pediatría, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Malaga 29010, Spain; Corresponding authors.Departamento de Fisiología Humana, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Malaga 29010, Spain; Corresponding authors.Departamento de Fisiología Humana, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Malaga 29010, SpainDepartamento de Farmacología y Pediatría, Facultad de Medicina, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Malaga 29010, SpainIntroduction: One of the hallmarks of Parkinsońs Disease (PD) is oxidative distress, leading to mitochondrial dysfunction and neurodegeneration. Insulin-like growth factor II (IGF-II) has been proven to have antioxidant and neuroprotective effects in some neurodegenerative diseases, including PD. Consequently, there is growing interest in understanding the different mechanisms involved in the neuroprotective effect of this hormone. Objectives: To clarify the mechanism of action of IGF-II involved in the protective effect of this hormone. Methods: The present study was carried out on a cellular model PD based on the incubation of dopaminergic cells (SN4741) in a culture with the toxic 1-methyl-4-phenylpyridinium (MPP+), in the presence of IGF-II. This model undertakes proteomic analyses in order to understand which molecular cell pathways might be involved in the neuroprotective effect of IGF-II. The most important proteins found in the proteomic study were tested by Western blot, colorimetric enzymatic activity assay and immunocytochemistry. Along with the proteomic study, mitochondrial morphology and function were also studied by transmission electron microscopy and oxygen consumption rate. The cell cycle was also analysed using 7AAd/BrdU staining, and flow cytometry. Results: The results obtained indicate that MPP+, MPP++IGF-II treatment and IGF-II, when compared to control, modified the expression of 197, 246 proteins and 207 respectively. Some of these proteins were found to be involved in mitochondrial structure and function, and cell cycle regulation. Including IGF-II in the incubation medium prevents the cell damage induced by MPP+, recovering mitochondrial function and cell cycle dysregulation, and thereby decreasing apoptosis. Conclusion: IGF-II improves mitochondrial dynamics by promoting the association of Mitofilin with mitochondria, regaining function and redox homeostasis. It also rebalances the cell cycle, reducing the amount of apoptosis and cell death by the regulation of transcription factors, such as Checkpoint kinase 1.http://www.sciencedirect.com/science/article/pii/S2090123224000493Parkinsońs diseaseIGF-IINeuroprotectionMitochondriaCell cycle |
| spellingShingle | Silvana-Yanina Romero-Zerbo Nadia Valverde Silvia Claros Pablo Zamorano-Gonzalez Federica Boraldi Francesco-Demetrio Lofaro Estrella Lara Jose Pavia Maria Garcia-Fernandez Belen Gago Elisa Martin-Montañez New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson’s disease Journal of Advanced Research Parkinsońs disease IGF-II Neuroprotection Mitochondria Cell cycle |
| title | New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson’s disease |
| title_full | New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson’s disease |
| title_fullStr | New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson’s disease |
| title_full_unstemmed | New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson’s disease |
| title_short | New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson’s disease |
| title_sort | new molecular mechanisms to explain the neuroprotective effects of insulin like growth factor ii in a cellular model of parkinson s disease |
| topic | Parkinsońs disease IGF-II Neuroprotection Mitochondria Cell cycle |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000493 |
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