Search results for "Adrenoleukodystrophy"

showing 8 items of 18 documents

Fibrate induction of the adrenoleukodystrophy-related gene (ABCD2)

2001

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease due to a defect in the ABCD1 (ALD) gene. ABCD1, and the two close homologues ABCD2 (ALDR) and ABCD3 (PMP70), are genes encoding ATP-binding cassette half-transporters of the peroxisomal membrane. As overexpression of the ABCD2 or ABCD3 gene can reverse the biochemical phenotype of X-ALD (reduced beta-oxidation of very-long-chain fatty acids), pharmacological induction of these partially redundant genes may represent a therapeutic approach to X-ALD. We previously reported that the ABCD2 and ABCD3 genes could be strongly induced by fibrates, which are hypolipidaemic drugs and peroxisome-proliferators in rodents. We provide e…

MaleTranscription GeneticMolecular Sequence DataResponse elementReceptors Cytoplasmic and NuclearATP-binding cassette transporterATP Binding Cassette Transporter Subfamily DBiochemistryMiceFenofibrateABCD3Sequence Homology Nucleic AcidABCD2medicineAnimalsHumansRats WistarAdrenoleukodystrophyPromoter Regions GeneticGeneHypolipidemic AgentsMice KnockoutBase SequencebiologyDNATransfectionPeroxisomemedicine.diseaseMolecular biologyRatsGene Expression Regulationbiology.proteinATP-Binding Cassette TransportersAdrenoleukodystrophyTranscription FactorsEuropean Journal of Biochemistry
researchProduct

Evaluation of the therapeutic potential of PPARalpha agonists for X-linked adrenoleukodystrophy.

2003

Adrenoleukodystrophy protein (ABCD1), a peroxisomal membrane protein, is mutated in patients affected by X-linked adrenoleukodystrophy (X-ALD). Adrenoleukodystrophy-related protein (ABCD2) is the closest relative of ABCD1. Pharmacological induction of ABCD2 gene expression has been proposed as a novel therapy strategy for X-ALD. Fibrates induce peroxisome proliferation and Abcd2 expression in rodent liver. Here we evaluate the possibility of using peroxisome proliferator-activated receptor alpha (PPARalpha) agonists for pharmacological induction of ABCD2 expression. In the liver of PPARalpha-deficient mice, both the constitutive and the fenofibrate-inducible Abcd2 gene expression was found …

Malemedicine.medical_specialtyEndocrinology Diabetes and MetabolismMolecular Sequence DataDrug Evaluation PreclinicalPeroxisome ProliferationReceptors Cytoplasmic and NuclearBiologySulfidesATP Binding Cassette Transporter Subfamily DResponse ElementsBiochemistrychemistry.chemical_compoundMiceEndocrinologyInternal medicineGene expressionGeneticsmedicineAnimalsAdrenoleukodystrophyMolecular BiologyGenePhenylurea CompoundsTetradecylthioacetic acidBrainmedicine.diseaseMolecular biologyIntronsMice Mutant StrainsSterol regulatory element-binding proteinDNA-Binding ProteinsMice Inbred C57BLButyratesSterolsEndocrinologychemistryGene Expression RegulationLiverCCAAT-Enhancer-Binding ProteinsSterol Regulatory Element Binding Protein 1AdrenoleukodystrophyATP-Binding Cassette TransportersSterol regulatory element-binding protein 2Sterol Regulatory Element Binding Protein 1Sterol Regulatory Element Binding Protein 2Transcription FactorsMolecular genetics and metabolism
researchProduct

Pharmacological Induction of Redundant Genes for a Therapy of X-ALD

2003

X-linked adrenoleukodystrophy (X-ALD) is a recessive neurologic disease with an incidence among males of 1/17 000. Since the identification of the X-ALD gene (ABCD1) ten years ago (Mosser et al 1993), no satisfactory therapy has been available. A close homologue (ABCD2) was then cloned and presented as a putative modifier gene that could account for some of the extreme phenotypic variability of X-ALD (Lombard-Platet et al 1996). The inducibility of Abcd2 by the hypolipidemic drug fenofibrate in the liver of rodents (Albet et al 1997), correlated to a partial normalisation of the biochemical phenotype of X-ALD (Netik et al 1999), opened up the way of a pharmacological therapy of X-ALD. The b…

Pristanic acidcongenital hereditary and neonatal diseases and abnormalitiesFenofibrateendocrine system diseasesPharmacological therapybiologyPharmacologymedicine.diseasePhenylbutyrateBiochemical phenotypechemistry.chemical_compoundchemistrymedicineABCD2biology.proteinAdrenoleukodystrophyGenemedicine.drug
researchProduct

The four murine peroxisomal ABC-transporter genes differ in constitutive, inducible and developmental expression.

1999

Four ATP-binding cassette (ABC) half-transporters have been identified in mammalian peroxisomes: adrenoleukodystrophy protein (ALDP), adrenoleukodystrophy-related protein (ALDRP), 70-kDa peroxisomal membrane protein (PMP70) and PMP70-related protein (P70R). Inherited defects in ALDP cause the neurodegenerative disorder X-linked adrenoleukodystrophy (X-ALD). By comparative Northern blot analyses we found each of the four murine peroxisomal ABC transporter mRNA species at maximum abundance only in a few tissues, which differed for each family member. The four genes were also regulated differentially during mouse brain development: ALDP mRNA was most abundant in embryonic brain and gradually d…

Response elementMolecular Sequence DataATP-binding cassette transporterMice Inbred StrainsBiologyATP Binding Cassette Transporter Subfamily DBiochemistryATP Binding Cassette Transporter Subfamily D Member 1MiceFenofibrateGene expressionmedicinePeroxisomesAnimalsNorthern blotATP Binding Cassette Transporter Subfamily B Member 1RNA MessengerPromoter Regions GeneticGeneHypolipidemic AgentsMice KnockoutMessenger RNABrainGene Expression Regulation DevelopmentalMembrane ProteinsProteinsBiological Transportmedicine.diseaseMolecular biologyNuclear receptorLiverAdrenoleukodystrophyATP-Binding Cassette TransportersEuropean journal of biochemistry
researchProduct

Substrate specificity overlap and interaction between Adrenoleukodystrophy protein (ALDP/ABCD1) and Adrenoleukodystrophy-related protein (ALDRP/ABCD2)

2011

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by mutations in the ABCD1 gene, which encodes a peroxisomal member of the ATP-binding cassette (ABC) transporter subfamily D called ALDP. ALDP is supposed to function as a homodimer allowing the entry of CoA-esters of very-long chain fatty acids (VLCFA) into the peroxisome, the unique site of their β-oxidation. ALDP deficiency can be corrected by overexpression of ALDRP, its closest homolog. However, the exact nature of the substrates transported by ALDRP and its relationships with ALDP still remain unclear. To gain insight into the function of ALDRP, we used cell models allowing the induction in a dose-dependent m…

congenital hereditary and neonatal diseases and abnormalitiesendocrine system diseasesATP-binding cassette transportermembrane proteinsBiologyATP Binding Cassette Transporter Subfamily DBiochemistry03 medical and health sciences0302 clinical medicineabc transporterCell Line TumormedicineAnimals[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Molecular BiologyBeta oxidationfatty acid oxidation030304 developmental biologychemistry.chemical_classification0303 health sciencesadrenoleukodystrophyabc transporter;fatty acid;fatty acid oxidation;membrane proteins;peroxisomes;adrenoleukodystrophyFatty AcidsNeurosciencesWild typeFatty acidnutritional and metabolic diseasesperoxisomesCell BiologyPeroxisomemedicine.diseaseLipidsRatschemistryMembrane proteinBiochemistry[ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Neurons and CognitionATP-Binding Cassette TransportersAdrenoleukodystrophy[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]fatty acidOxidation-Reduction030217 neurology & neurosurgeryPolyunsaturated fatty acid
researchProduct

Evidence of oxidative stress in very long chain fatty acid--treated oligodendrocytes and potentialization of ROS production using RNA interference-di…

2011

X-linked adrenoleukodystrophy (X-ALD) and pseudo neonatal adrenoleukodystrophy (P-NALD) are neurodegenerative demyelinating diseases resulting from the functional loss of the peroxisomal ATP-binding cassette transporter D (ABCD1) and from single peroxisomal enzyme deficiency (Acyl-CoA oxidase1: ACOX1), respectively. As these proteins are involved in the catabolism of very long chain fatty acids (VLCFA: C24:0, C26:0), X-ALD and P-NALD patients are characterized by the accumulation of VLCFA in plasma and tissues. Since peroxisomes are involved in the metabolism of reactive oxygen species (ROS) and nitrogen species (RNS), we examined the impact of VLCFA on the oxidative status of 158N murine o…

congenital hereditary and neonatal diseases and abnormalitiesendocrine systemendocrine system diseasesVery long chain fatty acidBlotting Westernmedicine.disease_causeReal-Time Polymerase Chain ReactionTransfectionATP Binding Cassette Transporter Subfamily D Member 1Gas Chromatography-Mass SpectrometrySuperoxide dismutaseLipid peroxidationchemistry.chemical_compoundMicemedicinePeroxisomesAnimalsAdrenoleukodystrophyCells Culturedchemistry.chemical_classificationReactive oxygen speciesbiologyReverse Transcriptase Polymerase Chain ReactionGeneral NeuroscienceFatty Acidsnutritional and metabolic diseasesPeroxisomemedicine.diseaseFlow CytometryOligodendrogliaOxidative StressBiochemistrychemistryGene Knockdown Techniquesbiology.proteinACOX1AdrenoleukodystrophyATP-Binding Cassette TransportersRNA InterferenceAcyl-CoA OxidaseReactive Oxygen SpeciesOxidation-ReductionOxidative stressNeuroscience
researchProduct

Modulation of peroxisomes abundance by argan oil and lipopolysaccharides in acyl-CoA oxidase 1-deficient fibroblasts

2013

Pseudo-neonatal adrenoleukodystrophy (P-NALD) is a neurodegenerative disorder caused by acyl-CoA oxidase 1 (ACOX1) deficiency with subsequent impairment of peroxisomal fatty acid β-oxidation, accumulation of very long chain fatty acids (VLCFAs) and strong reduction in peroxisome abundance. Increase in peroxisome number has been previously suggested to improve peroxisomal disorders, and in this perspective, the present work was aimed at exploring whether modulation of peroxisomes abundance could be achieved in P-NALD fibroblasts. Here we showed that treatment with the natural Argan oil induced peroxisome proliferation in P-NALD fibroblasts. This induction was independent on activations of bo…

food.ingredientChemistryArgan oilPeroxisome ProliferationPeroxisomemedicine.diseaseCell biologyfoodPeroxisomal disordermedicineAcyl-CoA oxidaseACOX1AdrenoleukodystrophyPeroxisome proliferator-activated receptor alphaHealth
researchProduct

Induction of the adrenoleukodystrophy-related gene (ABCD2) by thyromimetics.

2009

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 (ALD) gene. The ABCD2 gene, its closest homolog, has been shown to compensate for ABCD1 deficiency when overexpressed. We previously demonstrated that the ABCD2 promoter contains a functional thyroid hormone response element. Thyroid hormone (T3) through its receptor TRbeta can induce hepatic Abcd2 expression in rodents and transiently normalize the VLCFA level in fibroblasts of Abcd1 null mice. In a therapeutic perspective, the use of selective agonists of TRbeta should present the advantage to be devoid of side effects, at least concerning the cardiotoxicity associated to TRalpha activation. I…

medicine.medical_specialtyThyroid HormonesEndocrinology Diabetes and MetabolismClinical BiochemistryBiologyAcetatesATP Binding Cassette Transporter Subfamily DTransfectionBiochemistryEndocrinologyDownregulation and upregulationPhenolsInternal medicinePeroxisomal disorderGene expressionChlorocebus aethiopsmedicineAnimalsHumansReceptorAdrenoleukodystrophyMolecular BiologyHormone response elementReporter geneGlyoxylatesCell BiologyTransfectionmedicine.diseaseCell biologyRatsUp-RegulationEndocrinologyCOS CellsMolecular MedicineTriiodothyronineAdrenoleukodystrophyATP-Binding Cassette TransportersThe Journal of steroid biochemistry and molecular biology
researchProduct