0000000000010496

AUTHOR

Claudia Prinzen

showing 8 related works from this author

A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model

2004

Alzheimer disease (AD) is characterized by excessive deposition of amyloid beta-peptides (A beta peptides) in the brain. In the nonamyloidogenic pathway, the amyloid precursor protein (APP) is cleaved by the alpha-secretase within the A beta peptide sequence. Proteinases of the ADAM family (adisintegrin and metalloproteinase) are the main candidates as physiologically relevant alpha-secretases, but early lethality of knockout animals prevented a detailed analysis in neuronal cells. To overcome this restriction, we have generated transgenic mice that overexpress either ADAM10 or a catalytically inactive ADAM10 mutant. In this report we show that a moderate neuronal overexpression of ADAM10 i…

Genetically modified mousePathologymedicine.medical_specialtyAmyloidAmyloidADAM10BACE1-ASGene ExpressionMice TransgenicHippocampusArticleAmyloid beta-Protein PrecursorMiceAlzheimer DiseaseEndopeptidasesAmyloid precursor proteinmedicineAnimalsAspartic Acid EndopeptidasesHumansbiologybusiness.industryP3 peptideAmyloidosisGeneral Medicinemedicine.diseaseCell biologyEnzyme ActivationDisease Models AnimalCommentarybiology.proteinErratumAlzheimer's diseaseAmyloid Precursor Protein SecretasesbusinessAmyloid precursor protein secretaseJournal of Clinical Investigation
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P3‐335: Upstream of N‐ras (UNR) is involved in translational control of ADAM10 protein expression

2008

Background: The amyloid beta peptide (A ) is derived by proteolytic processing of the amyloid precursor protein (APP) by the beta-secretase BACE1 and gamma-secretase. In contrast to this amyloidogenic processing, APP is predominantly cleaved by the alpha-secretase within the A domain and this precludes the formation of A . We and other research groups could show that BACE1 protein expression is regulated by the 5’untranslated region (UTR) of the BACE1 mRNA, however little is known about the regulation of alpha-secretase. Similar to the 5’UTR of BACE1, the 5’UTR of ADAM10 consists of 444 nucleotides with a GC-content of 70% and two upstream open reading frames. We hypothesize that ADAM10, th…

Untranslated regionMessenger RNAbiologyEpidemiologyChemistryHealth PolicyADAM10RNA-binding proteinDNA-binding proteinCell biologyPsychiatry and Mental healthCellular and Molecular NeuroscienceDevelopmental NeuroscienceTranslational regulationAmyloid precursor proteinbiology.proteinNeurology (clinical)Geriatrics and GerontologyBinding siteAlzheimer's & Dementia
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Up-regulation of the α-Secretase Pathway

2007

α secretasebiologyDownregulation and upregulationChemistryAmyloid precursor proteinbiology.proteinPAC1 ReceptorCell biology
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Statins and the squalene synthase inhibitor zaragozic acid stimulate the non-amyloidogenic pathway of amyloid-beta protein precursor processing by su…

2010

Cholesterol-lowering drugs such as statins influence the proteolytic processing of the amyloid-beta protein precursor (AbetaPP) and are reported to stimulate the activity of alpha-secretase, the major preventive secretase of Alzheimer's disease. Statins can increase the alpha-secretase activity by their cholesterol-lowering properties as well as by impairment of isoprenoids synthesis. In the present study, we elucidate the contribution of these pathways in alpha-secretase activation. We demonstrate that zaragozic acid, a potent inhibitor of squalene synthase which blocks cholesterol synthesis but allows synthesis of isoprenoids, also stimulates alpha-secretase activity. Treatment of human n…

ADAM10Blotting Westernchemistry.chemical_compoundSqualeneADAM10 ProteinAmyloid beta-Protein PrecursorCell Line TumormedicineHumansLovastatinRNA Small InterferingProtein precursorLuciferasesLipid raftNeuronsbiologyATP synthaseChemistryReverse Transcriptase Polymerase Chain ReactionTerpenesGeneral NeuroscienceAnticholesteremic AgentsCell MembraneMembrane ProteinsTricarboxylic AcidsZaragozic acidGeneral MedicineBridged Bicyclo Compounds HeterocyclicEnzyme ActivationPsychiatry and Mental healthClinical PsychologyADAM ProteinsCholesterolFarnesyl-Diphosphate FarnesyltransferaseBiochemistrybiology.proteinlipids (amino acids peptides and proteins)LovastatinGeriatrics and GerontologyAmyloid Precursor Protein SecretasesHydroxymethylglutaryl-CoA Reductase InhibitorsAmyloid precursor protein secretasemedicine.drugJournal of Alzheimer's disease : JAD
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[S2‐01‐01]: Alpha‐secretase as a therapeutic target

2005

Psychiatry and Mental healthCellular and Molecular NeuroscienceDevelopmental NeuroscienceAlpha secretaseEpidemiologyChemistryHealth PolicyCancer researchNeurology (clinical)Geriatrics and GerontologyAlzheimer's & Dementia
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Expression of the Anti-amyloidogenic Secretase ADAM10 Is Suppressed by Its 5′-Untranslated Region*

2010

Proteolytic processing of the amyloid precursor protein by alpha-secretase prevents formation of the amyloid beta-peptide (Abeta), which is the main constituent of amyloid plaques in brains of Alzheimer disease (AD) patients. alpha-Secretase activity is decreased in AD, and overexpression of the alpha-secretase ADAM10 (a disintegrin and metalloprotease 10) in an AD animal model prevents amyloid pathology. ADAM10 has a 444-nucleotide-long, very GC-rich 5'-untranslated region (5'-UTR) with two upstream open reading frames. Because similar properties of 5'-UTRs are found in transcripts of many genes, which are regulated by translational control mechanisms, we asked whether ADAM10 expression is…

Five prime untranslated regionenzymology [Brain]ADAM10ADAM10 protein humanBACE1-ASgenetics [Amyloid Precursor Protein Secretases]genetics [Alzheimer Disease]genetics [ADAM Proteins]BiochemistryGene Expression Regulation Enzymologicbiosynthesis [Membrane Proteins]ADAM10 ProteinAlzheimer DiseaseChlorocebus aethiopsAmyloid precursor proteinProtein biosynthesisbiosynthesis [Amyloid beta-Peptides]genetics [Amyloid beta-Peptides]AnimalsHumansGene RegulationMolecular BiologySequence Deletionbiosynthesis [ADAM Proteins]Amyloid beta-PeptidesbiologyBase SequenceP3 peptideenzymology [Alzheimer Disease]BrainMembrane ProteinsCell BiologyMolecular biologyBiochemistry of Alzheimer's diseasegenetics [Membrane Proteins]ADAM Proteinsbiosynthesis [Amyloid Precursor Protein Secretases]Protein Biosynthesisddc:540COS Cellsbiology.proteinAmyloid Precursor Protein Secretases5' Untranslated RegionsAmyloid precursor protein secretase
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P2‐307: A stable G‐quadruplex within the ADAM10 5'‐UTR is involved in translational repression of ADAM10

2011

Psychiatry and Mental healthCellular and Molecular NeuroscienceDevelopmental NeuroscienceFive prime untranslated regionEpidemiologyTranslational repressionChemistryHealth PolicyADAM10Neurology (clinical)Geriatrics and GerontologyG-quadruplexCell biologyAlzheimer's & Dementia
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Genomic structure and functional characterization of the human ADAM10 promoter

2005

The ADAM10 gene encodes a membrane-bound disintegrin-metalloproteinase, which, after overexpression in an Alzheimer disease (AD) mouse model, prevents amyloid pathology and improves long-term potentiation and memory. Because enhancing ADAM10 expression appears to be a reasonable approach for treatment of AD, we functionally analyzed the ADAM10 gene. Both human and mouse ADAM10 genes comprise approximately 160 kbp, are composed of 16 exons, and are evolutionarily highly conserved within 500 bp upstream of either translation initiation site. By using luciferase reporter assays, we demonstrate that nucleotides -2179 to -1 upstream of the human ADAM10 translation initiation site represent a fun…

5' Flanking Region5' flanking regionTretinoinBiologyPolymorphism Single NucleotideBiochemistryCell LineConserved sequenceADAM10 ProteinMiceOpen Reading FramesExonAlzheimer DiseaseGeneticsAnimalsHumansPromoter Regions GeneticMolecular BiologyTranscription factorGeneConserved SequenceExpressed Sequence TagsIntronMembrane ProteinsPromoterExonsMolecular biologyIntronsADAM ProteinsOpen reading frameMutagenesis Site-DirectedAmyloid Precursor Protein SecretasesBiotechnologyThe FASEB Journal
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