Search results for "BETA-PROTEIN"

showing 3 items of 73 documents

Regulated Proteolysis of RAGE and AβPP as Possible Link Between Type 2 Diabetes Mellitus and Alzheimer's Disease

2009

Epidemiological studies have linked type 2 diabetes mellitus (T2DM) with an increased risk of developing Alzheimer's disease (AD). In T2DM, the elevated blood glucose level promotes formation of advanced glycation end products (AGEs). The receptor for AGEs (RAGE) is a type I membrane-protein and is also able to import amyloid-beta (Abeta) from the blood across the blood-brain-barrier into the brain. Oligomeric Abeta peptides disturb synaptic function in the brain and are believed to contribute to the development of AD. Abeta peptides are released from the amyloid-beta protein precursor (AbetaPP) after sequential proteolysis by beta- and gamma-secretases but alpha-secretase-mediated cleavage…

medicine.medical_specialtyendocrine system diseasesProteolysisReceptor for Advanced Glycation End ProductsAmyloid beta-Protein PrecursorAlzheimer DiseaseGlycationInternal medicinemental disordersmedicineAnimalsHumansReceptors ImmunologicProtein precursorProtein kinase AReceptorAmyloid beta-Peptidesmedicine.diagnostic_testChemistryGeneral Neurosciencenutritional and metabolic diseasesGeneral MedicinePsychiatry and Mental healthClinical PsychologyCholesterolEndocrinologyDiabetes Mellitus Type 2EctodomainPeptide transportAmyloid Precursor Protein SecretasesGeriatrics and GerontologySignal transductionJournal of Alzheimer's Disease
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α-secretase mediated conversion of the amyloid precursor protein derived membrane stub C99 to C83 limits Aβ generation

2009

The Swedish mutation within the amyloid precursor protein (APP) causes early-onset Alzheimer's disease due to increased cleavage of APP by BACE1. While beta-secretase shedding of Swedish APP (APPswe) largely results from an activity localized in the late secretory pathway, cleavage of wild-type APP occurs mainly in endocytic compartments. However, we show that liberation of Abeta from APPswe is still dependent on functional internalization from the cell surface. Inspite the unchanged overall beta-secretase cleaved soluble APP released from APP(swe) secretion, mutations of the APPswe internalization motif strongly reduced C99 levels and substantially decreased Abeta secretion. We point out t…

medicine.medical_specialtymedia_common.quotation_subjectEndocytic cycleCHO CellsTransfectionBiochemistryAmyloid beta-Protein PrecursorCellular and Molecular NeuroscienceCricetulusCricetinaeInternal medicinemental disordersmedicineAmyloid precursor proteinAnimalsHumansBiotinylationProtein Interaction Domains and MotifsSecretionInternalizationSecretory pathwaymedia_commonAmyloid beta-PeptidesbiologyChemistryP3 peptidePeptide FragmentsCell biologyEndocrinologyGene Expression RegulationAlpha secretaseMutationbiology.proteinAmyloid Precursor Protein SecretasesAmyloid precursor protein secretaseJournal of Neurochemistry
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Metalloprotease meprin beta generates nontoxic N-terminal amyloid precursor protein fragments in vivo.

2011

Identification of physiologically relevant substrates is still the most challenging part in protease research for understanding the biological activity of these enzymes. The zinc-dependent metalloprotease meprin β is known to be expressed in many tissues with functions in health and disease. Here, we demonstrate unique interactions between meprin β and the amyloid precursor protein (APP). Although APP is intensively studied as a ubiquitously expressed cell surface protein, which is involved in Alzheimer disease, its precise physiological role and relevance remain elusive. Based on a novel proteomics technique termed terminal amine isotopic labeling of substrates (TAILS), APP was identified …

medicine.medical_treatmentBiologyProteomicsBiochemistryPolymerase Chain ReactionCell LineSubstrate Specificity03 medical and health sciencesAmyloid beta-Protein PrecursorMice0302 clinical medicinemental disordersAmyloid precursor proteinmedicineAnimalsHumansProtein IsoformsMolecular Biology030304 developmental biologyDNA Primerschemistry.chemical_classification0303 health sciencesMetalloproteinaseProteaseBase SequenceNeurodegenerationTioproninBrainCell BiologyTerminal amine isotopic labeling of substratesmedicine.diseaseIn vitroRecombinant Proteins3. Good healthMice Inbred C57BLEnzymechemistryBiochemistryProtein Synthesis and Degradationbiology.protein030217 neurology & neurosurgeryThe Journal of biological chemistry
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