Ferroptosis is an iron-dependent cell death caused by impaired glutathione metabolism, lipid peroxidation and mitochondrial failure. Emerging evidences report a role for ferroptosis in Friedreich's Ataxia (FRDA), a neurodegenerative disease caused by the decreased expression of the mitochondrial protein frataxin. Nrf2 signalling is implicated in many molecular aspects of ferroptosis, by upstream regulating glutathione homeostasis, mitochondrial function and lipid metabolism. As Nrf2 is down-regulated in FRDA, targeting Nrf2-mediated ferroptosis in FRDA may be an attractive option to counteract neurodegeneration in such disease, thus paving the way to new therapeutic opportunities. In this study, we evaluated ferroptosis hallmarks in frataxin-silenced mouse myoblasts, in hearts of a frataxin Knockin/Knockout (KIKO) mouse model, in skin fibroblasts and blood of patients, particularly focusing on ferroptosis-driven gene expression, mitochondrial impairment and lipid peroxidation. The efficacy of Nrf2 inducers to neutralize ferroptosis has been also evaluated.

La Rosa, P., Petrillo, S., Turchi, R., Berardinelli, F., Schirinzi, T., Vasco, G., et al. (2021). The Nrf2 induction prevents ferroptosis in Friedreich's Ataxia. REDOX BIOLOGY, 38, 101791 [10.1016/j.redox.2020.101791].

The Nrf2 induction prevents ferroptosis in Friedreich's Ataxia

Schirinzi, Tommaso;Lettieri-Barbato, Daniele;Aquilano, Katia;
2021-01-01

Abstract

Ferroptosis is an iron-dependent cell death caused by impaired glutathione metabolism, lipid peroxidation and mitochondrial failure. Emerging evidences report a role for ferroptosis in Friedreich's Ataxia (FRDA), a neurodegenerative disease caused by the decreased expression of the mitochondrial protein frataxin. Nrf2 signalling is implicated in many molecular aspects of ferroptosis, by upstream regulating glutathione homeostasis, mitochondrial function and lipid metabolism. As Nrf2 is down-regulated in FRDA, targeting Nrf2-mediated ferroptosis in FRDA may be an attractive option to counteract neurodegeneration in such disease, thus paving the way to new therapeutic opportunities. In this study, we evaluated ferroptosis hallmarks in frataxin-silenced mouse myoblasts, in hearts of a frataxin Knockin/Knockout (KIKO) mouse model, in skin fibroblasts and blood of patients, particularly focusing on ferroptosis-driven gene expression, mitochondrial impairment and lipid peroxidation. The efficacy of Nrf2 inducers to neutralize ferroptosis has been also evaluated.
1-gen-2021
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
Settore BIO/09 - FISIOLOGIA
English
EPI-743
Ferroptosis
Friedreich ataxia
Lipid peroxides
Mitochondria
Nrf2
Redox imbalance
Sulforaphane
La Rosa, P., Petrillo, S., Turchi, R., Berardinelli, F., Schirinzi, T., Vasco, G., et al. (2021). The Nrf2 induction prevents ferroptosis in Friedreich's Ataxia. REDOX BIOLOGY, 38, 101791 [10.1016/j.redox.2020.101791].
La Rosa, P; Petrillo, S; Turchi, R; Berardinelli, F; Schirinzi, T; Vasco, G; Lettieri-Barbato, D; Fiorenza, Mt; Bertini, Es; Aquilano, K; Piemonte, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/259842
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