title: Metal Homeostasis Regulators Suppress FRDA Phenotypes in a Drosophila Model of the Disease.
abstract: 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.
authors.affiliation: Department of Genetics, University of Valencia, Burjassot, Valencia, Spain.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Sirena
authors.initials: S
authors.lastname: Soriano
authors.affiliation: Department of Genetics, University of Valencia, Burjassot, Valencia, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Calap-Quintana
authors.affiliation: Department of Genetics, University of Valencia, Burjassot, Valencia, Spain.
authors.forename: José Vicente
authors.initials: JV
authors.lastname: Llorens
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Ismael
authors.initials: I
authors.lastname: Al-Ramahi
authors.affiliation: Department of Biomaterials and Bioinspired Materials, Instituto de Ciencia de Materiales de Madrid/CSIC, Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Gutiérrez
authors.affiliation: Department of Genetics, University of Valencia, Burjassot, Valencia, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Martínez-Sebastián
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Juan
authors.initials: J
authors.lastname: Botas
authors.affiliation: Department of Genetics, University of Valencia, Burjassot, Valencia, Spain.|CIBERSAM, INCLIVA, Valencia, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Moltó
mesh_terms: D000535:Aluminum / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D003300:Copper / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics*; D005621:Friedreich Ataxia / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000235:genetics; D008345:Manganese / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D014157:Transcription Factors / Q000235:genetics*; D015032:Zinc / Q000378:metabolism; D000096923:Frataxin; D000097809:Transcription Factor MTF-1
chemical_list: D000535:Aluminum; D000975:Antioxidants; D002352:Carrier Proteins; D003300:Copper; D004268:DNA-Binding Proteins; D007501:Iron; D033862:Iron-Binding Proteins; D008345:Manganese; D014157:Transcription Factors; D015032:Zinc; D000096923:Frataxin; D000097809:Transcription Factor MTF-1; C017800:zinc-binding protein