The Nrf2 induction prevents ferroptosis in Friedreich's Ataxia.

Redox Biology
Piergiorgio La RosaFiorella Piemonte

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.

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·Isabel Lastres-BeckerÁngeles Martin-Requero
Jul 25, 2021·Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi·Sara PetrilloFiorella Piemonte

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Methods Mentioned

BETA
transfection
biopsies
PCR
ELISA
Assay
fluorescence microscopy
nuclear translocation

Software Mentioned

Graphpad
Prism
Image Lab

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