TY - JOUR A2 - Gomes, Cláudio M. AU - Seguin, Alexandra AU - Monnier, Véronique AU - Palandri, Amandine AU - Bihel, Frédéric AU - Rera, Michael AU - Schmitt, Martine AU - Camadro, Jean-Michel AU - Tricoire, Hervé AU - Lesuisse, Emmanuel PY - 2015 DA - 2015/10/11 TI - A Yeast/Drosophila Screen to Identify New Compounds Overcoming Frataxin Deficiency SP - 565140 VL - 2015 AB - Friedreich’s ataxia (FA) is a rare neurodegenerative disease which is very debilitating for the patients who progressively lose their autonomy. The lack of efficient therapeutic treatment of the disease strongly argues for urgent need to search for new active compounds that may stop the progression of the disease or prevent the appearance of the symptoms when the genetic defect is diagnosed early enough. In the present study, we used a yeast strain with a deletion of the frataxin homologue gene as a model of FA cells in a primary screen of two chemical libraries, a fraction of the French National Chemical Library (5500 compounds) and the Prestwick collection (880 compounds). We ran a secondary screen on Drosophila melanogaster flies expressing reduced levels of frataxin during larval development. Half of the compounds selected in yeast appeared to be active in flies in this developmental paradigm, and one of the two compounds with highest activities in this assay partially rescued the heart dilatation phenotype resulting from heart specific depletion of frataxin. The unique complementarity of these two frataxin-deficient models, unicellular and multicellular, appears to be very efficient to select new compounds with improved selectivity, bringing significant perspectives towards improvements in FA therapy. SN - 1942-0900 UR - https://doi.org/10.1155/2015/565140 DO - 10.1155/2015/565140 JF - Oxidative Medicine and Cellular Longevity PB - Hindawi Publishing Corporation KW - ER -