TY - JOUR
T1 - Metal homeostasis regulators suppress FRDA phenotypes in a drosophila model of the disease
AU - Soriano, Sirena
AU - Calap-Quintana, Pablo
AU - Llorens, José Vicente
AU - Al-Ramahi, Ismael
AU - Gutiérrez, Lucía
AU - Martínez-Sebastián, María José
AU - Botas, Juan
AU - Moltó, María Dolores Moltó
N1 - Publisher Copyright:
© 2016 Soriano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/7
Y1 - 2016/7
N2 - Friedreich's ataxia (FRDA), the most commonly inherited ataxia in populations of European origin, is a neurodegenerative disorder caused by a decrease in frataxin levels. One of the hallmarks of the disease is the accumulation of iron in several tissues including the brain, and frataxin has been proposed to play a key role in iron homeostasis. We found that the levels of zinc, copper, manganese and aluminum were also increased in a Drosophila model of FRDA, and that copper and zinc chelation improve their impaired motor performance. By means of a candidate genetic screen, we identified that genes implicated in iron, zinc and copper transport and metal detoxification can restore frataxin deficiency-induced phenotypes. Taken together, these results demonstrate that the metal dysregulation in FRDA includes other metals besides iron, therefore providing a new set of potential therapeutic targets.
AB - Friedreich's ataxia (FRDA), the most commonly inherited ataxia in populations of European origin, is a neurodegenerative disorder caused by a decrease in frataxin levels. One of the hallmarks of the disease is the accumulation of iron in several tissues including the brain, and frataxin has been proposed to play a key role in iron homeostasis. We found that the levels of zinc, copper, manganese and aluminum were also increased in a Drosophila model of FRDA, and that copper and zinc chelation improve their impaired motor performance. By means of a candidate genetic screen, we identified that genes implicated in iron, zinc and copper transport and metal detoxification can restore frataxin deficiency-induced phenotypes. Taken together, these results demonstrate that the metal dysregulation in FRDA includes other metals besides iron, therefore providing a new set of potential therapeutic targets.
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U2 - 10.1371/journal.pone.0159209
DO - 10.1371/journal.pone.0159209
M3 - Article
C2 - 27433942
AN - SCOPUS:84979224946
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e0159209
ER -