Search results for "amyloid"

showing 10 items of 494 documents

Effect of a dominant-negative form of ADAM10 in a mouse model of Alzheimer's disease.

2009

The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid-beta protein precursor (AbetaPP) within the region of the amyloid-beta peptides to prevent their formation and aggregation in the brain. Members of the ADAM family (a disintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. We recently demonstrated that overexpression of ADAM10 in mice transgenic for human AbetaPP (ADAM10 x APP[V717I]) alleviated functional deficits related to Alzheimer's disease. To further demonstrate that this is due to the specific activity of alpha-secretase, we characterized mice overexpressing an inactive form of ADAM10 (ADAM10[E384A]; ADAM10-dn). T…

ADAM10Morris water navigation taskGlutamic AcidStimulationMice TransgenicADAM10 ProteinAmyloid beta-Protein PrecursorMiceIn vivoAlzheimer DiseaseDisintegrinReaction TimeAnimalsHumansIsoleucineProtein precursorMaze LearningSwimmingMetalloproteinaseAlaninebiologyBehavior AnimalChemistryGeneral NeuroscienceAge FactorsMembrane ProteinsValineGeneral MedicineCell biologyMice Inbred C57BLPsychiatry and Mental healthClinical PsychologyADAM ProteinsDisease Models Animalbiology.proteinSpecific activityGeriatrics and GerontologyAmyloid Precursor Protein SecretasesJournal of Alzheimer's disease : JAD
researchProduct

Down-regulation of Endogenous Amyloid Precursor Protein Processing due to Cellular Aging

2005

Processing of amyloid precursor protein (APP) is a well acknowledged central pathogenic mechanism in Alzheimer disease. However, influences of age-associated cellular alterations on the biochemistry of APP processing have not been studied in molecular detail so far. Here, we report that processing of endogenous APP is down-regulated during the aging of normal human fibroblasts (IMR-90). The generation of intracellular APP cleavage products C99, C83, and AICD gradually declines with increasing life span and is accompanied by a reduced secretion of soluble APP (sAPP) and sAPPalpha. Further, the maturation of APP was reduced in senescent cells, which has been shown to be directly mediated by a…

ADAM10NicastrinEndogenyBiochemistryCell LineAmyloid beta-Protein PrecursorMembrane MicrodomainsDownregulation and upregulationEndopeptidasesmental disordersPresenilin-1Amyloid precursor proteinAspartic Acid EndopeptidasesHumansSecretionMolecular BiologyCellular SenescenceMembrane GlycoproteinsbiologyChemistryMembrane ProteinsCell BiologyFibroblastsCholesterolBiochemistrybiology.proteinAmyloid Precursor Protein SecretasesProtein Processing Post-TranslationalAmyloid precursor protein secretaseIntracellularJournal of Biological Chemistry
researchProduct

Alpha-secretase as a therapeutic target.

2007

In the non-amyloidogenic pathway the alpha-secretase cleaves the amyloid precursor protein (APP) within the sequence of Abeta-peptides and precludes their formation. In addition, alpha-secretase cleavage releases an N-terminal extracellular domain with neurotrophic and neuroprotective properties. The disintegrin metalloproteinase ADAM10 has been shown to act as alpha-secretase in vivo, to prevent amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. An increase in alpha-secretase activity therefore is an attractive strategy for treatment of AD and may be achieved by modulating selective signalling pathways. Functional characterization of the human ADAM10 prom…

ADAM10Retinoic acidModels BiologicalReceptors G-Protein-Coupledchemistry.chemical_compoundADAM10 ProteinDownregulation and upregulationAlzheimer DiseaseExtracellularAmyloid precursor proteinAnimalsHumansTranscription factorG protein-coupled receptorbiologyMembrane ProteinsCell biologyEnzyme ActivationADAM ProteinsDisease Models AnimalNeurologychemistryAlpha secretasebiology.proteinNeurology (clinical)Amyloid Precursor Protein SecretasesCurrent Alzheimer research
researchProduct

Fibrillation of Human Serum Albumin at physiological pH is inhibited by oxidation

2014

AMyloid oxidation disease spectroscopy TEM
researchProduct

Binding mode analysis of ABCA7 for the prediction of novel Alzheimer's disease therapeutics

2021

Graphical abstract

ATP Adenosine-triphosphateNBD nucleotide binding domainGSH reduced glutathionePolypharmacologyAlzheimer’s disease (AD)ATP-binding cassette transporterHTS high-throughput screeningBiochemistryABCA7Structural BiologyPLIF protein ligand interactionMSD membrane spanning domainPDB protein data bankTM transmembrane helixABC ATP-binding cassetteMultitarget modulation (PANABC)RMSD root mean square distanceABC transporter (ABCA1 ABCA4 ABCA7)Computer Science ApplicationsMOE Molecular Operating EnvironmentPharmacophoreSNP single-nucleotide polymorphismBiotechnologyResearch ArticleBBB blood-brain barrierBiophysicsDrug designComputational biologyBiologyAD Alzheimer’s diseasePET positron emission tomographyIC intracellular helixAPP amyloid precursor proteincryo-EM cryogenic-electron microscopyGeneticsHomology modelingBinding siteRational drug design and developmentComputingMethodologies_COMPUTERGRAPHICSNBD-cholesterol 7-nitro-2-13-benzoxadiazol-4-yl-cholesterolTransporterPSO particle swarm optimizationPET tracer (PETABC)ECD extracellular domainR-domain/region regulatory domain/regionABCA1biology.proteinEH extracellular helixTP248.13-248.65BODIPY-cholesterol 44-difluoro-4-bora-3a4a-diaza-s-indacene-cholesterolComputational and Structural Biotechnology Journal
researchProduct

Interconnected mechanism in Abeta(1-40) peptide fibril formation

2011

Abeta(1-40)Amyloid fibril
researchProduct

ThT influences Abeta(1-40) aggregation process

2013

Abeta(1-40)Amyloid fibrilSettore FIS/07 - Fisica Applicata(Beni Culturali Ambientali Biol.e Medicin)
researchProduct

Topographic heterogeneity of amyloid B-protein epitopes in brains with various forms of neuronal ceroid lipofuscinoses suggesting defective processin…

1990

To verify our hypothesis of defective protease inhibitor domains that are encoded by abnormal processing of amyloid precursor protein (APP) in brains of patients with neuronal ceroid lipofuscinoses (NCL), immunohistochemical and cytochemical studies were performed with monoclonal antibodies (mAbs) directed against various domains of APP. For the studies, 22 autopsy brains were used: 12 with different forms of NCL, and 10 control brains. The staining procedure for the avidin-biotin complex (ABC) technique and the postembedding gold-labelled procedure for electron microscopy (EM) were employed. Of all mAbs used for the study, only mAbs generated against amyloid B-protein bound to neural tissu…

AdultAmyloidPathologymedicine.medical_specialtyBatten diseaseAdolescentAmyloidImmunocytochemistryPathology and Forensic MedicineLipofuscinEpitopes03 medical and health sciencesCellular and Molecular Neuroscience0302 clinical medicineNeuronal Ceroid-LipofuscinosesAmyloid precursor proteinmedicineHumansSenile plaquesChildAged030304 developmental biology0303 health sciencesAmyloid beta-PeptidesbiologyAntibodies MonoclonalBrainInfantMiddle Agedmedicine.diseaseImmunohistochemistryMolecular biology3. Good healthChild Preschoolbiology.proteinNeuronal ceroid lipofuscinosisNeurology (clinical)Protein Processing Post-Translational030217 neurology & neurosurgeryImmunostainingActa Neuropathologica
researchProduct

Cardiac MR enables diagnosis in 90% of patients with acute chest pain, elevated biomarkers and unobstructed coronary arteries

2015

To assess the diagnostic value of cardiac MRI (CMR) in patients with acute chest pain, elevated cardiac enzymes and a negative coronary angiogram.This study included a total of 125 patients treated in the chest pain unit during a 39-month period. Each included patient underwent MRI within a median of 3 days after cardiac catheterization. The MRI protocol comprised cine, oedema-sensitive and late gadolinium-enhancement imaging. The standard of reference was a consensus diagnosis based on clinical follow-up and the synopsis of all clinical, laboratory and imaging data.MRI revealed a multitude of diagnoses, including ischaemic cardiomyopathy (CM), dilated CM, myocarditis, Takotsubo CM, hyperte…

AdultGadolinium DTPAMalemedicine.medical_specialtyCardiac CatheterizationChest PainMyocarditismedicine.medical_treatmentContrast MediaMagnetic Resonance Imaging CineChest painCoronary AngiographyRisk AssessmentPredictive Value of TestsRisk FactorsInternal medicinemedicineHumansRadiology Nuclear Medicine and imagingMedical diagnosisCardiac catheterizationAgedAged 80 and overFull Paperbusiness.industryGeneral MedicineMiddle Agedmedicine.diseaseHypertensive heart diseaseCoronary arteriesmedicine.anatomical_structureCardiac amyloidosisCardiovascular DiseasesPredictive value of testscardiovascular systemCardiologyFemaleRadiologymedicine.symptombusinessBiomarkers
researchProduct

Pure Progressive Amnesia and the APPV717G Mutation

2009

We report an isolated, slowly progressive, pure amnestic phenotype in a 59-year-old member of a family affected by autosomal dominant familial Alzheimer disease. Early-onset Alzheimer disease in this family was associated with a V717G mutation in the amyloid precursor protein gene (APP). Subjective impairment of episodic memory began in our subject at the age of 44 years and subsequent, longitudinal neuropsychologic assessment confirmed progressive, severe, global impairment of memory functions over a period of 14 years with preservation of other cognitive domains. The mean annual hippocampal atrophy rate, determined by volumetric magnetic resonance imaging was intermediate between values p…

AdultMaleAgingPathologymedicine.medical_specialtyGlycineAmnesiaHippocampusAmyloid beta-Protein PrecursorAtrophyAlzheimer DiseasemedicineHumansDementiaMemory disorderEpisodic memoryAgedSettore M-PSI/02 - Psicobiologia E Psicologia FisiologicaCognitive disorderValineMiddle Agedmedicine.diseaseAPPV717G mutation.PedigreePsychiatry and Mental healthClinical PsychologyPhenotypeMutationDisease ProgressionPure progressive amnesiaFemaleAmnesiaAtrophyGeriatrics and Gerontologymedicine.symptomAlzheimer's diseasePsychologyGerontologyFrontotemporal dementia
researchProduct