Antioxidant amelioration of Riboflavin transporter deficiency in motoneurons derived from patient-specific induced pluripotent stem cells

Chiara Marioli, Valentina Magliocca, Stefania Petrini, Alessia Niceforo, Rossella Borghi, Sara Petrillo, Piergiorgio La Rosa, Fiorella Colasuonno, Tiziana Persichini, Fiorella Piemonte, Keith Massey, Marco Tartaglia, Sandra Moreno, Enrico Bertini, Claudia Compagnucci

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondrial dysfunction is a key element in the pathogenesis of neurodegenerative disorders, such as riboflavin transporter deficiency (RTD). This is a rare, childhood-onset disease characterized by motoneuron degeneration and caused by mutations in SLC52A2 and SLC52A3, encoding riboflavin (RF) transporters (RFVT2 and RFVT3, respectively), resulting in muscle weakness, ponto-bulbar paralysis and sensorineural deafness. Based on previous findings, which document the contribution of oxidative stress in RTD pathogenesis, we tested possible beneficial effects of several antioxidants (Vitamin C, Idebenone, Coenzyme Q10 and EPI-743, either alone or in combination with RF) on the morphology and function of neurons derived from induced pluripotent stem cells (iPSCs) from two RTD patients. To identify possible improvement of the neuronal morphotype, neurite length was measured by confocal microscopy after β-III tubulin immunofluorescent staining. Neuronal function was evaluated by determining superoxide anion generation by MitoSOX assay and intracellular calcium (Ca2+) levels, using the Fluo-4 probe. Among the antioxidants tested, EPI-743 restored the redox status, improved neurite length and ameliorated intracellular calcium influx into RTD motoneurons. In conclusion, we suggest that antioxidant supplementation may have a role in RTD treatment.

Original languageEnglish
Article number7402
Pages (from-to)1-17
Number of pages17
JournalInternational Journal of Molecular Sciences
Volume21
Issue number19
DOIs
Publication statusPublished - Oct 1 2020

Keywords

  • Antioxidants
  • IPSCs
  • Mitochondria
  • Motoneurons
  • Neurodegenerative disease
  • Oxidative stress
  • Riboflavin transporters
  • RTD syndrome

ASJC Scopus subject areas

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

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