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

Gil, Antonio Matos; Martín-Montañez, Elisa; Valverde, Nadia; Lara, Estrella; Boraldi, Federica; Claros, Silvia; Romero-Zerbo, Silvana Y.; Fernández, Óscar; Pavía, J.; García-Fernández, María

doi:10.3390/cells10010034

Cited by 9 publications

(6 citation statements)

References 71 publications

(107 reference statements)

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“…Altered levels of mitochondrial proteins were reported in retinal neurons in models of diabetic retinopathy [ 61 ] and glaucoma [ 62 ]. Results from our study are consistent with studies on neuroprotective properties of FTY in other models where FTY improved mitochondrial stability and restored mitochondrial dynamics under oxidative stress conditions [ 20 , 63 , 64 , 65 ]. Our present study did not investigate the changes in mitochondrial function.…”

Section: Discussionsupporting

confidence: 91%

Neuroprotective Effects of Fingolimod in a Cellular Model of Optic Neuritis

Candadai

Liu

Verma

et al. 2021

Cells

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Visual dysfunction resulting from optic neuritis (ON) is one of the most common clinical manifestations of multiple sclerosis (MS), characterized by loss of retinal ganglion cells, thinning of the nerve fiber layer, and inflammation to the optic nerve. Current treatments available for ON or MS are only partially effective, specifically target the inflammatory phase, and have limited effects on long-term disability. Fingolimod (FTY) is an FDA-approved immunomodulatory agent for MS therapy. The objective of the current study was to evaluate the neuroprotective properties of FTY in the cellular model of ON-associated neuronal damage. R28 retinal neuronal cell damage was induced through treatment with tumor necrosis factor-α (TNFα). In our cell viability analysis, FTY treatment showed significantly reduced TNFα-induced neuronal death. Treatment with FTY attenuated the TNFα-induced changes in cell survival and cell stress signaling molecules. Furthermore, immunofluorescence studies performed using various markers indicated that FTY treatment protects the R28 cells against the TNFα-induced neurodegenerative changes by suppressing reactive oxygen species generation and promoting the expression of neuronal markers. In conclusion, our study suggests neuroprotective effects of FTY in an in vitro model of optic neuritis.

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Section: Discussionsupporting

confidence: 91%

Neuroprotective Effects of Fingolimod in a Cellular Model of Optic Neuritis

Candadai

Liu

Verma

et al. 2021

Cells

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“…PD and emotional stress are strongly related to ROS production, with mitochondria being one of the major sources of energy and ROS production [4,5,20,23,24,36]. In this combined model of PD and mild to moderate stress, as in other mitochondrial toxic situations in neuronal cell cultures [23,24,34,38], we found decreases in mitochondrial function measured as m∆Ψ and cellular bioenergetic parameters. The current study showed decreases in m∆Ψ after the administration of CORT alone and MPP + alone, in agreement with other studies [23,24,40,42], and the effect was potentiated by these drugs' co-administration (Figure 2b).…”

Section: Discussionmentioning

confidence: 55%

“…A Seahorse Bioscience XF24 analyser (Agilent Technologies, Santa Clara, CA, USA) was used to measure the mitochondrial O 2 consumption rate (OCR) [37,38]. Cells were seeded in the specific 24-well plates (20,000 per well).…”

Section: Mitochondrial Oxygen Consumption Ratementioning

confidence: 99%

Impact of Glucocorticoid on a Cellular Model of Parkinson’s Disease: Oxidative Stress and Mitochondrial Function

et al. 2021

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Stress seems to contribute to the neuropathology of Parkinson’s disease (PD), possibly by dysregulation of the hypothalamic–pituitary–adrenal axis. Oxidative distress and mitochondrial dysfunction are key factors involved in the pathophysiology of PD and neuronal glucocorticoid-induced toxicity. Animal PD models have been generated to study the effects of hormonal stress, but no in vitro model has yet been developed. Our aim was to examine the impact of corticosterone (CORT) administration on a dopaminergic neuronal cell model of PD induced by the neurotoxin MPP+, as a new combined PD model based on the marker of endocrine response to stress, CORT, and oxidative-mitochondrial damage. We determined the impact of CORT, MPP+ and their co-incubation on reactive oxygen species production (O2−•), oxidative stress cellular markers (advanced-oxidation protein products and total antioxidant status), mitochondrial function (mitochondrial membrane potential and mitochondrial oxygen consumption rate) and neurodegeneration (Fluoro-Jade staining). Accordingly, the administration of MPP+ or CORT individually led to cell damage compared to controls (p < 0.05), as determined by several methods, whereas their co-incubation produced strong cell damage (p < 0.05). The combined model described here could be appropriate for investigating neuropathological hallmarks and for evaluating potential new therapeutic tools for PD patients suffering mild to moderate emotional stress.

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“…Mitochondrial O 2 consumption rate (OCR) was monitored in real time using the Seahorse Bioscience XF24 analyser (Agilent Technologies, Santa Clara, CA, USA) [ 40 , 41 ]. Cells were seeded in 24-well plates (20,000 cells/well), washed with PBS, and then incubated with Agilent Seahorse XF Base Medium (without phenol red and bicarbonate) (590 µL) containing pyruvate (1 mM) and glucose (25 mM).…”

Section: Methodsmentioning

confidence: 99%

Insulin-like Growth Factor II Prevents MPP+ and Glucocorticoid Mitochondrial-Oxidative and Neuronal Damage in Dopaminergic Neurons

et al. 2021

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Stress seems to contribute to Parkinson’s disease (PD) neuropathology, probably by dysregulation of the hypothalamic–pituitary–adrenal axis. Key factors in this pathophysiology are oxidative stress and mitochondrial dysfunction and neuronal glucocorticoid-induced toxicity. The insulin-like growth factor II (IGF-II), a pleiotropic hormone, has shown antioxidant and neuroprotective effects in some neurodegenerative disorders. Our aim was to examine the protective effect of IGF-II on a dopaminergic cellular combined model of PD and mild to moderate stress measuring oxidative stress parameters, mitochondrial and neuronal markers, and signalling pathways. IGF-II counteracts the mitochondrial-oxidative damage produced by the toxic synergistic effect of corticosterone and 1-methyl-4-phenylpyridinium, 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. Thus, IGF-II is a potential therapeutic tool for treatment and prevention of disease progression in PD patients suffering mild to moderate emotional stress.

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

Cited by 9 publications

References 71 publications

Neuroprotective Effects of Fingolimod in a Cellular Model of Optic Neuritis

Neuroprotective Effects of Fingolimod in a Cellular Model of Optic Neuritis

Impact of Glucocorticoid on a Cellular Model of Parkinson’s Disease: Oxidative Stress and Mitochondrial Function

Insulin-like Growth Factor II Prevents MPP+ and Glucocorticoid Mitochondrial-Oxidative and Neuronal Damage in Dopaminergic Neurons

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