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Nrf2-Inducers Counteract Neurodegeneration in Frataxin-Silenced Motor Neurons: Disclosing New Therapeutic Targets for Friedreich's Ataxia
Journal article   Open access   Peer reviewed

Nrf2-Inducers Counteract Neurodegeneration in Frataxin-Silenced Motor Neurons: Disclosing New Therapeutic Targets for Friedreich's Ataxia

Sara Petrillo, Emanuela Piermarini, Anna Pastore, Gessica Vasco, Tommaso Schirinzi, Rosalba Carrozzo, Enrico Bertini and Fiorella Piemonte
International journal of molecular sciences, v 18(10), p2173
18 Oct 2017
DOI: https://doi.org/10.3390/ijms18102173
PMID: 29057804
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.3390/ijms18102173View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Adolescent Adult Cells, Cultured Child Female Fibroblasts - drug effects Fibroblasts - metabolism Friedreich Ataxia - metabolism Friedreich Ataxia - pathology Humans Iron-Binding Proteins - genetics Isothiocyanates - pharmacology Isothiocyanates - therapeutic use Male Motor Neurons - drug effects Motor Neurons - metabolism Motor Neurons - pathology Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism Oxidative Stress
Oxidative stress is actively involved in Friedreich's Ataxia (FA), thus pharmacological targeting of the antioxidant machinery may have therapeutic value. Here, we analyzed the relevance of the antioxidant phase II response mediated by the transcription factor Nrf2 on frataxin-deficient cultured motor neurons and on fibroblasts of patients. The in vitro treatment of the potent Nrf2 activator sulforaphane increased Nrf2 protein levels and led to the upregulation of phase II antioxidant enzymes. The neuroprotective effects were accompanied by an increase in neurites' number and extension. Sulforaphane (SFN) is a natural compound of many diets and is now being used in clinical trials for other pathologies. Our results provide morphological and biochemical evidence to endorse a neuroprotective strategy that may have therapeutic relevance for FA. The findings of this work reinforce the crucial importance of Nrf2 in FA and provide a rationale for using Nrf2-inducers as pharmacological agents.

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
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