Nrf2 Induction Re-establishes a Proper Neuronal Differentiation Program in Friedreich’s Ataxia Neural Stem Cells
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...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2019-07-01
|
Series: | Frontiers in Cellular Neuroscience |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00356/full |
id |
doaj-79d80e1d975545b793836397bec7c5f5 |
---|---|
record_format |
Article |
spelling |
doaj-79d80e1d975545b793836397bec7c5f52020-11-25T01:50:28ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-07-011310.3389/fncel.2019.00356472684Nrf2 Induction Re-establishes a Proper Neuronal Differentiation Program in Friedreich’s Ataxia Neural Stem CellsPiergiorgio La Rosa0Marta Russo1Jessica D’Amico2Sara Petrillo3Katia Aquilano4Daniele Lettieri-Barbato5Daniele Lettieri-Barbato6Riccardo Turchi7Enrico S. Bertini8Fiorella Piemonte9Unit of Neuromuscular and Neurodegenerative Diseases, IRCCS Bambino Gesù Children’s Hospital, Rome, ItalyUnit of Neuromuscular and Neurodegenerative Diseases, IRCCS Bambino Gesù Children’s Hospital, Rome, ItalyUnit of Neuromuscular and Neurodegenerative Diseases, IRCCS Bambino Gesù Children’s Hospital, Rome, ItalyUnit of Neuromuscular and Neurodegenerative Diseases, IRCCS Bambino Gesù Children’s Hospital, Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Rome, ItalyIRCCS Fondazione Santa Lucia, Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Rome, ItalyUnit of Neuromuscular and Neurodegenerative Diseases, IRCCS Bambino Gesù Children’s Hospital, Rome, ItalyUnit of Neuromuscular and Neurodegenerative Diseases, IRCCS Bambino Gesù Children’s Hospital, Rome, ItalyFrataxin 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.https://www.frontiersin.org/article/10.3389/fncel.2019.00356/fullNrf2Friedreich’s Ataxianeural stem cellsfrataxinneurogenesisantioxidant |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Piergiorgio La Rosa Marta Russo Jessica D’Amico Sara Petrillo Katia Aquilano Daniele Lettieri-Barbato Daniele Lettieri-Barbato Riccardo Turchi Enrico S. Bertini Fiorella Piemonte |
spellingShingle |
Piergiorgio La Rosa Marta Russo Jessica D’Amico Sara Petrillo Katia Aquilano Daniele Lettieri-Barbato Daniele Lettieri-Barbato Riccardo Turchi Enrico S. Bertini Fiorella Piemonte Nrf2 Induction Re-establishes a Proper Neuronal Differentiation Program in Friedreich’s Ataxia Neural Stem Cells Frontiers in Cellular Neuroscience Nrf2 Friedreich’s Ataxia neural stem cells frataxin neurogenesis antioxidant |
author_facet |
Piergiorgio La Rosa Marta Russo Jessica D’Amico Sara Petrillo Katia Aquilano Daniele Lettieri-Barbato Daniele Lettieri-Barbato Riccardo Turchi Enrico S. Bertini Fiorella Piemonte |
author_sort |
Piergiorgio La Rosa |
title |
Nrf2 Induction Re-establishes a Proper Neuronal Differentiation Program in Friedreich’s Ataxia Neural Stem Cells |
title_short |
Nrf2 Induction Re-establishes a Proper Neuronal Differentiation Program in Friedreich’s Ataxia Neural Stem Cells |
title_full |
Nrf2 Induction Re-establishes a Proper Neuronal Differentiation Program in Friedreich’s Ataxia Neural Stem Cells |
title_fullStr |
Nrf2 Induction Re-establishes a Proper Neuronal Differentiation Program in Friedreich’s Ataxia Neural Stem Cells |
title_full_unstemmed |
Nrf2 Induction Re-establishes a Proper Neuronal Differentiation Program in Friedreich’s Ataxia Neural Stem Cells |
title_sort |
nrf2 induction re-establishes a proper neuronal differentiation program in friedreich’s ataxia neural stem cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2019-07-01 |
description |
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. |
topic |
Nrf2 Friedreich’s Ataxia neural stem cells frataxin neurogenesis antioxidant |
url |
https://www.frontiersin.org/article/10.3389/fncel.2019.00356/full |
work_keys_str_mv |
AT piergiorgiolarosa nrf2inductionreestablishesaproperneuronaldifferentiationprograminfriedreichsataxianeuralstemcells AT martarusso nrf2inductionreestablishesaproperneuronaldifferentiationprograminfriedreichsataxianeuralstemcells AT jessicadamico nrf2inductionreestablishesaproperneuronaldifferentiationprograminfriedreichsataxianeuralstemcells AT sarapetrillo nrf2inductionreestablishesaproperneuronaldifferentiationprograminfriedreichsataxianeuralstemcells AT katiaaquilano nrf2inductionreestablishesaproperneuronaldifferentiationprograminfriedreichsataxianeuralstemcells AT danielelettieribarbato nrf2inductionreestablishesaproperneuronaldifferentiationprograminfriedreichsataxianeuralstemcells AT danielelettieribarbato nrf2inductionreestablishesaproperneuronaldifferentiationprograminfriedreichsataxianeuralstemcells AT riccardoturchi nrf2inductionreestablishesaproperneuronaldifferentiationprograminfriedreichsataxianeuralstemcells AT enricosbertini nrf2inductionreestablishesaproperneuronaldifferentiationprograminfriedreichsataxianeuralstemcells AT fiorellapiemonte nrf2inductionreestablishesaproperneuronaldifferentiationprograminfriedreichsataxianeuralstemcells |
_version_ |
1725001734379536384 |