Metal homeostasis regulators suppress FRDA phenotypes in a drosophila model of the disease

6533b7dafe1ef96bd126e3e8

RESEARCH PRODUCT

Metal homeostasis regulators suppress FRDA phenotypes in a drosophila model of the disease

María Dolores Moltó José Vicente Llorens Lucía Gutiérrez M. J. Martínez-sebastián Sirena Soriano Sirena Soriano Juan Botas Ismael Al-ramahi Pablo Calap-quintana

subject

0301 basic medicine Physiology Gene Expression lcsh:Medicine Mitochondrion medicine.disease_cause Antioxidants Iron-Binding Proteins Medicine and Health Sciences Homeostasis lcsh:Science Genetics Multidisciplinary biology Drosophila Melanogaster Iron-binding proteins Animal Models Phenotype Mitochondria 3. Good health Insects DNA-Binding Proteins Chemistry Zinc Phenotypes Physical Sciences Drosophila Anatomy medicine.symptom Drosophila melanogaster Research Article Chemical Elements Ataxia Arthropoda Iron Research and Analysis Methods 03 medical and health sciences Model Organisms Ocular System medicine Genetics Animals Humans Genetik Manganese lcsh:R Organisms Biology and Life Sciences Cell Biology biology.organism_classification Invertebrates Oxidative Stress Disease Models Animal 030104 developmental biology Friedreich Ataxia Frataxin biology.protein Eyes lcsh:Q Physiological Processes Carrier Proteins Head Copper Oxidative stress Aluminum Transcription Factors Genetic screen

description

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.

year	journal	country	edition	language
2016-07-19

10.1371/journal.pone.0159209 http://hdl.handle.net/10261/186981