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Review

The NRF2 Signaling Network Defines Clinical Biomarkers and Therapeutic Opportunity in Friedreich’s Ataxia

Unit of Muscular and Neurodegenerative Diseases, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy
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Int. J. Mol. Sci. 2020, 21(3), 916; https://doi.org/10.3390/ijms21030916
Received: 27 December 2019 / Revised: 27 January 2020 / Accepted: 29 January 2020 / Published: 30 January 2020
(This article belongs to the Special Issue Peripheral Biomarkers in Neurodegenerative Diseases)
Friedreich’s ataxia (FA) is a trinucleotide repeats expansion neurodegenerative disorder, for which no cure or approved therapies are present. In most cases, GAA trinucleotide repetitions in the first intron of the FXN gene are the genetic trigger of FA, determining a strong reduction of frataxin, a mitochondrial protein involved in iron homeostasis. Frataxin depletion impairs iron–sulfur cluster biosynthesis and determines iron accumulation in the mitochondria. Mounting evidence suggests that these defects increase oxidative stress susceptibility and reactive oxygen species production in FA, where the pathologic picture is worsened by a defective regulation of the expression and signaling pathway modulation of the transcription factor NF-E2 p45-related factor 2 (NRF2), one of the fundamental mediators of the cellular antioxidant response. NRF2 protein downregulation and impairment of its nuclear translocation can compromise the adequate cellular response to the frataxin depletion-dependent redox imbalance. As NRF2 stability, expression, and activation can be modulated by diverse natural and synthetic compounds, efforts have been made in recent years to understand if regulating NRF2 signaling might ameliorate the pathologic defects in FA. Here we provide an analysis of the pharmaceutical interventions aimed at restoring the NRF2 signaling network in FA, elucidating specific biomarkers useful for monitoring therapeutic effectiveness, and developing new therapeutic tools. View Full-Text
Keywords: Friedreich’s ataxia; NRF2; redox active drugs; frataxin; neurodegenerative diseases Friedreich’s ataxia; NRF2; redox active drugs; frataxin; neurodegenerative diseases
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MDPI and ACS Style

La Rosa, P.; Bertini, E.S.; Piemonte, F. The NRF2 Signaling Network Defines Clinical Biomarkers and Therapeutic Opportunity in Friedreich’s Ataxia. Int. J. Mol. Sci. 2020, 21, 916. https://doi.org/10.3390/ijms21030916

AMA Style

La Rosa P, Bertini ES, Piemonte F. The NRF2 Signaling Network Defines Clinical Biomarkers and Therapeutic Opportunity in Friedreich’s Ataxia. International Journal of Molecular Sciences. 2020; 21(3):916. https://doi.org/10.3390/ijms21030916

Chicago/Turabian Style

La Rosa, Piergiorgio, Enrico S. Bertini, and Fiorella Piemonte. 2020. "The NRF2 Signaling Network Defines Clinical Biomarkers and Therapeutic Opportunity in Friedreich’s Ataxia" International Journal of Molecular Sciences 21, no. 3: 916. https://doi.org/10.3390/ijms21030916

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