Search results for "Serpins"

showing 3 items of 23 documents

On the molecular structure of human neuroserpin polymers

2012

The polymerization of serpins is at the root of a large class of diseases; the molecular structure of serpin polymers has been recently debated. In this work, we study the polymerization kinetics of human neuroserpin by Fourier Transform Infra Red spectroscopy and by time-lapse Size Exclusion Chromatography. First, we show that two distinct neuroserpin polymers, formed at 45 and 85°C, display the same isosbestic points in the Amide I' band, and therefore share common secondary structure features. We also find a concentration independent polymerization rate at 45°C suggesting that the polymerization rate-limiting step is the formation of an activated monomeric species. The polymer structures…

Models MolecularSize-exclusion chromatographySerpinBiochemistryProtein Structure Secondaryserpinopathieprotein aggregationchemistry.chemical_compoundStructural BiologyNeuroserpinCatalytic DomainSpectroscopy Fourier Transform InfraredPolymer chemistryHumansMolecular BiologyProtein secondary structureSerpinschemistry.chemical_classificationIsosbestic pointChemistryNeuropeptidesserpinPolymerSettore FIS/07 - Fisica Applicata(Beni Culturali Ambientali Biol.e Medicin)KineticsCrystallographyMonomerprotein aggregation; serpins; serpinopathies; serpin polymerization; FTIRPolymerizationFTIRChromatography GelProtein Multimerizationserpin polymerization
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Functional and dysfunctional conformers of human neuroserpin characterized by optical spectroscopies and Molecular Dynamics

2015

Neuroserpin (NS) is a serine protease inhibitor (SERPIN) involved in different neurological pathologies, including the Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB), related to the aberrant polymerization of NS mutants. Here we present an in vitro and in silico characterization of native neuroserpin and its dysfunctional conformation isoforms: the proteolytically cleaved conformer, the inactive latent conformer, and the polymeric species. Based on circular dichroism and fluorescence spectroscopy, we present an experimental validation of the latent model and highlight the main structural features of the different conformers. In particular, emission spectra of aromatic res…

Protein FoldingCircular dichroismSerine Proteinase InhibitorsProtein ConformationStereochemistryNeuroserpinBiophysicsEpilepsies MyoclonicMolecular Dynamics SimulationSerpinMolecular DynamicsBiochemistryProtein Structure SecondaryArticleFluorescenceAnalytical ChemistryMolecular dynamicsProtein structureNeuroserpinmedicineHumansProtein IsoformsFluorescence emission spectra; circular dichroism; neuroserpin latent conformationneuroserpin latent conformationFamilial encephalopathy with neuroserpin inclusion bodiesMolecular BiologyConformational isomerismSerpinsFluorescence emission spectraSerpinChemistryCircular DichroismConformational diseaseNeuropeptidesHydrogen Bondingmedicine.diseaseSettore FIS/07 - Fisica Applicata(Beni Culturali Ambientali Biol.e Medicin)Heredodegenerative Disorders Nervous SystemProtein foldingBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics
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Pigment epithelium-derived factor is a niche signal for neural stem cell renewal.

2006

Adult stem cells are characterized by self-renewal and multilineage differentiation, and these properties seem to be regulated by signals from adjacent differentiated cell types and by extracellular matrix molecules, which collectively define the stem cell "niche." Self-renewal is essential for the lifelong persistence of stem cells, but its regulation is poorly understood. In the mammalian brain, neurogenesis persists in two germinal areas, the subventricular zone (SVZ) and the hippocampus, where continuous postnatal neuronal production seems to be supported by neural stem cells (NSCs). Here we show that pigment epithelium-derived factor (PEDF) is secreted by components of the murine SVZ a…

TelencephalonCellular differentiationSubventricular zoneBiologyHippocampusMicePEDFEpendymaLateral VentriclesChlorocebus aethiopsmedicineAnimalsHumansNerve Growth FactorsEye ProteinsCells CulturedSerpinsCell ProliferationInjections IntraventricularNeuronsNeuronal PlasticityGeneral NeuroscienceStem CellsNeurogenesisCell CycleCell DifferentiationNeural stem cellmedicine.anatomical_structurenervous systemCOS CellsEndothelium VascularStem cellNeuroscienceCell DivisionAstrocyteAdult stem cellSignal TransductionNature neuroscience
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