Nrf2 Induction Re-establishes a Proper Neuronal Differentiation Program in Friedreich’s Ataxia Neural Stem Cells

Piergiorgio La Rosa, Marta Russo, Jessica D’Amico, Sara Petrillo, Katia Aquilano, Daniele Lettieri-Barbato, Riccardo Turchi, Enrico S. Bertini, Fiorella Piemonte

Research output: Contribution to journalArticle

Abstract

Frataxin deficiency is the pathogenic cause of Friedreich’s Ataxia, an autosomal recessive disease characterized by the increase of oxidative stress and production of free radicals in the cell. Although the onset of the pathology occurs in the second decade of life, cognitive differences and defects in brain structure and functional activation are observed in patients, suggesting developmental defects to take place during fetal neurogenesis. Here, we describe impairments in proliferation, stemness potential and differentiation in neural stem cells (NSCs) isolated from the embryonic cortex of the Frataxin Knockin/Knockout mouse, a disease animal model whose slow-evolving phenotype makes it suitable to study pre-symptomatic defects that may manifest before the clinical onset. We demonstrate that enhancing the expression and activity of the antioxidant response master regulator Nrf2 ameliorates the phenotypic defects observed in NSCs, re-establishing a proper differentiation program.

Original languageEnglish
Article number356
JournalFrontiers in Cellular Neuroscience
Volume13
DOIs
Publication statusPublished - Jul 31 2019

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Keywords

  • antioxidant
  • frataxin
  • Friedreich’s Ataxia
  • neural stem cells
  • neurodegeneration
  • neurogenesis
  • Nrf2

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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