Frataxin deficiency leads to reduced expression and impaired translocation of NF-E2-Related factor (Nrf2) in cultured motor neurons

Valentina D'Oria, Stefania Petrini, Lorena Travaglini, Chiara Priori, Emanuela Piermarini, Sara Petrillo, Barbara Carletti, Enrico Bertini, Fiorella Piemonte

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Oxidative stress has been implicated in the pathogenesis of Friedreich's Ataxia (FRDA), a neurodegenerative disease caused by the decreased expression of frataxin, a mitochondrial protein responsible of iron homeostasis. Under conditions of oxidative stress, the activation of the transcription factor NF-E2-related factor (Nrf2) triggers the antioxidant cellular response by inducing antioxidant response element (ARE) driven genes. Increasing evidence supports a role for the Nrf2-ARE pathway in neurodegenerative diseases. In this study, we analyzed the expression and the distribution of Nrf2 in silenced neurons for frataxin gene. Decreased Nrf2 mRNA content and a defective activation after treatment with pro-oxidants have been evidenced in frataxin-silenced neurons by RT-PCR and confocal microscopy. The loss of Nrf2 in FRDA may greatly enhance the cellular susceptibility to oxidative stress and make FRDA neurons more vulnerable to injury. Our findings may help to focus on this promising target, especially in its emerging role in the neuroprotective response.

Original languageEnglish
Pages (from-to)7853-7865
Number of pages13
JournalInternational Journal of Molecular Sciences
Volume14
Issue number4
DOIs
Publication statusPublished - 2013

Fingerprint

Friedreich Ataxia
Oxidative stress
ataxia
Motor Neurons
Antioxidants
neurons
Antioxidant Response Elements
Neurodegenerative diseases
Neurons
antioxidants
Oxidative Stress
Chemical elements
Neurodegenerative Diseases
NF-E2 Transcription Factor
Genes
Chemical activation
genes
Transcription factors
Confocal microscopy
Mitochondrial Proteins

Keywords

  • Frataxin
  • FRDA
  • GSSG
  • Nrf2
  • NSC34 neurons
  • Oxidative stress

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Medicine(all)

Cite this

Frataxin deficiency leads to reduced expression and impaired translocation of NF-E2-Related factor (Nrf2) in cultured motor neurons. / D'Oria, Valentina; Petrini, Stefania; Travaglini, Lorena; Priori, Chiara; Piermarini, Emanuela; Petrillo, Sara; Carletti, Barbara; Bertini, Enrico; Piemonte, Fiorella.

In: International Journal of Molecular Sciences, Vol. 14, No. 4, 2013, p. 7853-7865.

Research output: Contribution to journalArticle

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AU - Priori, Chiara

AU - Piermarini, Emanuela

AU - Petrillo, Sara

AU - Carletti, Barbara

AU - Bertini, Enrico

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