0000000000356974

AUTHOR

Ismael Al-ramahi

showing 2 related works from this author

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

2016

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 def…

0301 basic medicinePhysiologyGene Expressionlcsh:MedicineMitochondrionmedicine.disease_causeAntioxidantsIron-Binding ProteinsMedicine and Health SciencesHomeostasislcsh:ScienceGeneticsMultidisciplinarybiologyDrosophila MelanogasterIron-binding proteinsAnimal ModelsPhenotypeMitochondria3. Good healthInsectsDNA-Binding ProteinsChemistryZincPhenotypesPhysical SciencesDrosophilaAnatomymedicine.symptomDrosophila melanogasterResearch ArticleChemical ElementsAtaxiaArthropodaIronResearch and Analysis Methods03 medical and health sciencesModel OrganismsOcular SystemmedicineGeneticsAnimalsHumansGenetikManganeselcsh:ROrganismsBiology and Life SciencesCell Biologybiology.organism_classificationInvertebratesOxidative StressDisease Models Animal030104 developmental biologyFriedreich AtaxiaFrataxinbiology.proteinEyeslcsh:QPhysiological ProcessesCarrier ProteinsHeadCopperOxidative stressAluminumTranscription FactorsGenetic screen
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TORC1 Inhibition by Rapamycin Promotes Antioxidant Defences in a Drosophila Model of Friedreich’s Ataxia

2015

Friedreich's ataxia (FRDA), the most common inherited ataxia in the Caucasian population, is a multisystemic disease caused by a significant decrease in the frataxin level. To identify genes capable of modifying the severity of the symptoms of frataxin depletion, we performed a candidate genetic screen in a Drosophila RNAi-based model of FRDA. We found that genetic reduction in TOR Complex 1 (TORC1) signalling improves the impaired motor performance phenotype of FRDA model flies. Pharmacologic inhibition of TORC1 signalling by rapamycin also restored this phenotype and increased the lifespan and ATP levels. Furthermore, rapamycin reduced the altered levels of malondialdehyde + 4-hydroxyalke…

Malelcsh:MedicineGene Expressionmedicine.disease_causeAntioxidantsAnimals Genetically ModifiedAdenosine Triphosphate0302 clinical medicineRNA interferenceIron-Binding ProteinsMalondialdehydeDrosophila Proteinslcsh:ScienceAconitate HydrataseGenetics0303 health sciencesMultidisciplinaryReverse Transcriptase Polymerase Chain ReactionGlutathione3. Good healthCell biologyDrosophila melanogasterRNA Interferencemedicine.symptomImmunosuppressive AgentsDrosophila ProteinResearch ArticleAtaxiaLongevityMotor ActivityBiologyAconitase03 medical and health sciencesmedicineAnimalsHumans030304 developmental biologySirolimusAldehydesSuperoxide Dismutaselcsh:RAutophagyRepressor ProteinsDisease Models AnimalOxidative StressFriedreich AtaxiaFrataxinbiology.proteinlcsh:Q030217 neurology & neurosurgeryOxidative stressTranscription FactorsGenetic screenPLOS ONE
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