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Article

Antioxidant Amelioration of Riboflavin Transporter Deficiency in Motoneurons Derived from Patient-Specific Induced Pluripotent Stem Cells

1
Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy
2
Department of Science, University Roma Tre, 00146 Rome, Italy
3
Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Department of Neuroscience, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy
4
Confocal Microscopy Core Facility, Research Laboratories, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy
5
Department of Science, LIME, University Roma Tre, 00146 Rome, Italy
6
Department of Psychology, Division of Neuroscience, Sapienza University of Rome, 00185 Rome, Italy
7
Science Director, Cure RTD Foundation, 6228 Northaven Rd., Dallas, TX 75230, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(19), 7402; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197402
Received: 31 August 2020 / Revised: 1 October 2020 / Accepted: 1 October 2020 / Published: 7 October 2020
(This article belongs to the Special Issue hiPSC-Derived Cells as Models for Drug Discovery)
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. View Full-Text
Keywords: neurodegenerative disease; motoneurons; mitochondria; oxidative stress; RTD syndrome; riboflavin transporters; antioxidants; iPSCs neurodegenerative disease; motoneurons; mitochondria; oxidative stress; RTD syndrome; riboflavin transporters; antioxidants; iPSCs
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MDPI and ACS Style

Marioli, C.; Magliocca, V.; Petrini, S.; Niceforo, A.; Borghi, R.; Petrillo, S.; La Rosa, P.; Colasuonno, F.; Persichini, T.; Piemonte, F.; Massey, K.; Tartaglia, M.; Moreno, S.; Bertini, E.; Compagnucci, C. Antioxidant Amelioration of Riboflavin Transporter Deficiency in Motoneurons Derived from Patient-Specific Induced Pluripotent Stem Cells. Int. J. Mol. Sci. 2020, 21, 7402. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197402

AMA Style

Marioli C, Magliocca V, Petrini S, Niceforo A, Borghi R, Petrillo S, La Rosa P, Colasuonno F, Persichini T, Piemonte F, Massey K, Tartaglia M, Moreno S, Bertini E, Compagnucci C. Antioxidant Amelioration of Riboflavin Transporter Deficiency in Motoneurons Derived from Patient-Specific Induced Pluripotent Stem Cells. International Journal of Molecular Sciences. 2020; 21(19):7402. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197402

Chicago/Turabian Style

Marioli, Chiara, 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, and Claudia Compagnucci. 2020. "Antioxidant Amelioration of Riboflavin Transporter Deficiency in Motoneurons Derived from Patient-Specific Induced Pluripotent Stem Cells" International Journal of Molecular Sciences 21, no. 19: 7402. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197402

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