Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage

Gil, Antonio; Martín-Montañez, Elisa; Valverde, Nadia; Lara, Estrella; Boraldi, Federica; Claros, Silvia; Romero-Zerbo, Silvana-Yanina; Fernández, Oscar; Pavia, Jose; Garcia-Fernandez, Maria

doi:10.3390/cells10010034

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Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage

Antonio Gil

^1,†,

Elisa Martín-Montañez

^1,2,†

^2,3,

^2,3,

⁴

^2,3,

Silvana-Yanina Romero-Zerbo

Oscar Fernández

^1,2,

Jose Pavia

^1,2,*,†

and

Maria Garcia-Fernandez

^2,3,*,†

Department of Pharmacology and Pediatrics, Faculty of Medicine, Malaga University, 29010 Malaga, Spain

Neuroscience Unit, Biomedical Research Institute of Malaga (IBIMA), Malaga University Hospital, 29010 Malaga, Spain

Department of Human Physiology, Faculty of Medicine, Malaga University, 29010 Malaga, Spain

⁴

Department of Life Sciences, University of Modena e Reggio Emilia, 41125 Modena, Italy

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Cells 2021, 10(1), 34; https://doi.org/10.3390/cells10010034

Received: 27 November 2020 / Revised: 21 December 2020 / Accepted: 24 December 2020 / Published: 29 December 2020

(This article belongs to the Special Issue Programmed Cell Death in Health and Disease)

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Abstract

Imbalance in the oxidative status in neurons, along with mitochondrial damage, are common characteristics in some neurodegenerative diseases. The maintenance in energy production is crucial to face and recover from oxidative damage, and the preservation of different sources of energy production is essential to preserve neuronal function. Fingolimod phosphate is a drug with neuroprotective and antioxidant actions, used in the treatment of multiple sclerosis. This work was performed in a model of oxidative damage on neuronal cell cultures exposed to menadione in the presence or absence of fingolimod phosphate. We studied the mitochondrial function, antioxidant enzymes, protein nitrosylation, and several pathways related with glucose metabolism and glycolytic and pentose phosphate in neuronal cells cultures. Our results showed that menadione produces a decrease in mitochondrial function, an imbalance in antioxidant enzymes, and an increase in nitrosylated proteins with a decrease in glycolysis and glucose-6-phosphate dehydrogenase. All these effects were counteracted when fingolimod phosphate was present in the incubation media. These effects were mediated, at least in part, by the interaction of this drug with its specific S1P receptors. These actions would make this drug a potential tool in the treatment of neurodegenerative processes, either to slow progression or alleviate symptoms. View Full-Text

Keywords: sphingosine-1-phosphate receptor analogue; fingolimod phosphate; neuroprotection; mitochondrial damage; glycolytic pathway; pentose phosphate pathway; redox homeostasis

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MDPI and ACS Style

Gil, A.; Martín-Montañez, E.; Valverde, N.; Lara, E.; Boraldi, F.; Claros, S.; Romero-Zerbo, S.-Y.; Fernández, O.; Pavia, J.; Garcia-Fernandez, M. Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage. Cells 2021, 10, 34. https://doi.org/10.3390/cells10010034

AMA Style

Gil A, Martín-Montañez E, Valverde N, Lara E, Boraldi F, Claros S, Romero-Zerbo S-Y, Fernández O, Pavia J, Garcia-Fernandez M. Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage. Cells. 2021; 10(1):34. https://doi.org/10.3390/cells10010034

Chicago/Turabian Style

Gil, Antonio, Elisa Martín-Montañez, Nadia Valverde, Estrella Lara, Federica Boraldi, Silvia Claros, Silvana-Yanina Romero-Zerbo, Oscar Fernández, Jose Pavia, and Maria Garcia-Fernandez. 2021. "Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage" Cells 10, no. 1: 34. https://doi.org/10.3390/cells10010034

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Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage

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