Metal Homeostasis Regulators Suppress FRDA Phenotypes in a Drosophila Model of the Disease
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 7, e0159209Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2016. Vol. 11, no 7, e0159209
IdentifiersURN: urn:nbn:se:uu:diva-304450DOI: 10.1371/journal.pone.0159209ISI: 000380169600039PubMedID: 27433942OAI: oai:DiVA.org:uu-304450DiVA: diva2:1033012
FunderEU, FP7, Seventh Framework Programme, 242193 EFACTSNIH (National Institute of Health), R01-NS42179