Nrf2-inducers counteract neurodegeneration in frataxin-silenced motor neurons: Disclosing new therapeutic targets for Friedreich’s Ataxia

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number2173
JournalInternational Journal of Molecular Sciences
Volume18
Issue number10
DOIs
Publication statusPublished - Oct 18 2017

Keywords

  • Dimethyl fumarate
  • Friedreich’s Ataxia
  • Inducers
  • Nrf2
  • Oxidative stress
  • Sulforaphane

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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