Search results for "Neurotrophic factors"

showing 10 items of 88 documents

Functions of histone modifications and histone modifiers in Schwann cells.

2019

Schwann cells (SCs) are the main glial cells present in the peripheral nervous system (PNS). Their primary functions are to insulate peripheral axons to protect them from the environment and to enable fast conduction of electric signals along big caliber axons by enwrapping them in a thick myelin sheath rich in lipids. In addition, SCs have the peculiar ability to foster axonal regrowth after a lesion by demyelinating and converting into repair cells that secrete neurotrophic factors and guide axons back to their former target to finally remyelinate regenerated axons. The different steps of SC development and their role in the maintenance of PNS integrity and regeneration after lesion are c…

0301 basic medicine570 Life sciencesLesionHistones03 medical and health sciencesCellular and Molecular Neuroscience0302 clinical medicineNeurotrophic factorsPeripheral Nerve InjuriesmedicineAnimalsHumansSecretionTranscription factorMyelin SheathbiologyRegeneration (biology)AxonsCell biologyNerve Regeneration030104 developmental biologyHistonemedicine.anatomical_structurenervous systemNeurologyMyelin sheathPeripheral nervous systembiology.proteinSchwann Cellsmedicine.symptom030217 neurology & neurosurgery570 BiowissenschaftenGliaREFERENCES
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Role of Regular Physical Activity in Neuroprotection against Acute Ischemia

2020

One of the major obstacles that prevents an effective therapeutic intervention against ischemic stroke is the lack of neuroprotective agents able to reduce neuronal damage; this results in frequent evolution towards a long-term disability with limited alternatives available to aid in recovery. Nevertheless, various treatment options have shown clinical efficacy. Neurotrophins such as brain-derived neurotrophic factor (BDNF), widely produced throughout the brain, but also in distant tissues such as the muscle, have demonstrated regenerative properties with the potential to restore damaged neural tissue. Neurotrophins play a significant role in both protection and recovery of function followi…

0301 basic medicineAngiogenesismyokinesphysical activityReviewneurotrophinsAntioxidantsBrain Ischemialcsh:Chemistry0302 clinical medicineNeurotrophic factorsneuronal recoverylcsh:QH301-705.5SpectroscopybiologyGeneral MedicineNeuroprotectionComputer Science ApplicationsAcute DiseaseNeurotrophinmedicine.symptomNeurotrophinTraumatic brain injuryIschemiaInflammationNeuroprotectionCatalysisInorganic Chemistry03 medical and health sciencesHormesisMyokineMyokinemedicineischemic strokeAnimalsHumansPhysical and Theoretical ChemistryExerciseMolecular Biologybusiness.industryOrganic Chemistrymedicine.disease030104 developmental biologylcsh:Biology (General)lcsh:QD1-999inflammationbiology.proteinBrain-derived neurotrophic factor (BDNF)businessNeuroscience030217 neurology & neurosurgeryInternational Journal of Molecular Sciences
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The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor

2021

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various in vitro and in vivo models of neuronal and non-neuronal damage. Although initially characterized as a secreted neurotrophic factor for midbrain dopamine neurons, MANF has recently gained more interest for its intracellular role in regulating the ER homeostasis, including serving as a cofactor of the chaperone glucose-regulated protein 78 (GRP78). We aimed for a better understanding of the neuroprotective mechanisms of MANF. Here we show for the first time that MANF promotes the survival of …

0301 basic medicineBiFC bimolecular fluorescence complementationMST microscale thermophoresisPDIA1 protein disulfide isomerase family A member 1ApoptosisNEUROTROPHIC FACTOR MANFEndoplasmic ReticulumBiochemistryprotein-protein interactionMiceBimolecular fluorescence complementationUPR unfolded protein responseENDOPLASMIC-RETICULUM STRESSMesencephalonNeurotrophic factorsInsulin-Secreting CellsProtein Interaction MappingBINDINGCOMPREHENSIVE RESOURCEATF6unfolded protein response (UPR)PDIA6 protein disulfide isomerase family A member 6PPIs protein-protein interactionsEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsNPTN neuroplastinbiologyChemistryapoptosisunfolded protein responsedopamine neurons3. Good healthCell biologyGDNF glial cell line–derived neurotrophic factorIRE1-ALPHASBD substrate-binding domainendoplasmic reticulum stressMANF mesencephalic astrocyte-derived neurotrophic factorTm tunicamycinneuroprotectionResearch ArticleProtein BindingSignal TransductionGRP78Protein Disulfide-Isomerase FamilyCell SurvivalTH tyrosine hydroxylasePrimary Cell CultureSCG superior cervical ganglionProtein Disulfide-IsomerasesIRE1 inositol-requiring enzyme 1ER-STRESSER endoplasmic reticulum03 medical and health sciencesohjelmoitunut solukuolemaC-MANF C-terminal domain of MANFCSPs chemical shift perturbationsAnimalsHumansHSP70 Heat-Shock ProteinsNerve Growth FactorsNBD nucleotide-binding domainNMR nuclear magnetic resonanceMolecular Biology030102 biochemistry & molecular biologyBIPATF6Dopaminergic NeuronsGene Expression ProfilingBinding proteinneuronal cell deathDISSOCIATIONCell BiologyNEI nucleotide exchange inhibitorEmbryo MammalianadenosiinitrifosfaattiATPhermosolutmesencephalic astrocyte-derived neurotrophic factorprotein–protein interactionPERK protein kinase RNA-like ER kinaseHEK293 Cells030104 developmental biologyGene Expression RegulationChaperone (protein)Tg thapsigarginbiology.proteinUnfolded protein responseAP-MS affinity purification mass spectrometry1182 Biochemistry cell and molecular biologyGFP-SH SH-tagged GFPendoplasmic reticulum stress (ER stress)DA dopaminemesencephalic astrocyte-derived neurotrophic factor (MANF)proteiinitNeuroplastin
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Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma

2018

Recurrent mutations in chromatin modifiers are specifically prevalent in adolescent or adult patients with Sonic hedgehog-associated medulloblastoma (SHH MB). Here, we report that mutations in the acetyltransferase CREBBP have opposing effects during the development of the cerebellum, the primary site of origin of SHH MB. Our data reveal that loss of Crebbp in cerebellar granule neuron progenitors (GNPs) during embryonic development of mice compromises GNP development, in part by downregulation of brain-derived neurotrophic factor (Bdnf). Interestingly, concomitant cerebellar hypoplasia was also observed in patients with Rubinstein-Taybi syndrome, a congenital disorder caused by germline mu…

0301 basic medicineCerebellumCrebbp protein mousemetabolism [Cerebellar Neoplasms]acetyltransferase; cerebellum; CREBBP; development; Rubinstein-Taybi syndrome; SHH medulloblastomagenetics [Hedgehog Proteins]MiceNeurotrophic factorsmetabolism [CREB-Binding Protein]Mice KnockoutNeuronsRubinstein-Taybi Syndromepathology [Rubinstein-Taybi Syndrome]CREBBPCREB-Binding ProteinPhenotypegenetics [CREB-Binding Protein]3. Good healthpathology [Cerebellar Neoplasms]acetyltransferasePhenotypemedicine.anatomical_structuregenetics [Rubinstein-Taybi Syndrome]Femalemetabolism [Hedgehog Proteins]Signal TransductionSHH medulloblastomaAdultcerebellumBiologyGeneral Biochemistry Genetics and Molecular BiologyCREBBP; Rubinstein-Taybi syndrome; SHH medulloblastoma; acetyltransferase; cerebellum; development.03 medical and health sciencesGermline mutationAcetyltransferasesmetabolism [Medulloblastoma]medicineAnimalsHumansgenetics [Cerebellar Neoplasms]Hedgehog Proteinsddc:610Cerebellar NeoplasmsdevelopmentMolecular BiologyMedulloblastomaRubinstein–Taybi syndromegenetics [Medulloblastoma]metabolism [Rubinstein-Taybi Syndrome]pathology [Medulloblastoma]Cell Biologymedicine.disease030104 developmental biologyMutationphysiology [CREB-Binding Protein]Cancer researchSHH protein humanCerebellar hypoplasia (non-human)metabolism [Acetyltransferases]CREBBP protein humanMedulloblastomaDevelopmental BiologyCongenital disorderDevelopmental Cell
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Regulation of Dendritic Spine Morphology in Hippocampal Neurons by Copine-6.

2015

Dendritic spines compartmentalize information in the brain, and their morphological characteristics are thought to underly synaptic plasticity. Here we identify copine-6 as a novel modulator of dendritic spine morphology. We found that brain-derived neurotrophic factor (BDNF) - a molecule essential for long-term potentiation of synaptic strength - upregulated and recruited copine-6 to dendritic spines in hippocampal neurons. Overexpression of copine-6 increased mushroom spine number and decreased filopodia number, while copine-6 knockdown had the opposite effect and dramatically increased the number of filopodia, which lacked PSD95. Functionally, manipulation of post-synaptic copine-6 level…

0301 basic medicineDendritic spineVesicular Inhibitory Amino Acid Transport Proteinsdrug effects [Synapses]Tropomyosin receptor kinase BHippocampal formationgenetics [Carrier Proteins]pharmacology [Brain-Derived Neurotrophic Factor]Hippocampusmetabolism [Vesicular Inhibitory Amino Acid Transport Proteins]Mtap2 protein ratMice0302 clinical medicineNeurotrophic factorsdrug effects [Synaptic Vesicles]genetics [Nerve Tissue Proteins]Cells Culturedultrastructure [Neurons]NeuronsChemistryLong-term potentiationSynaptic Potentialsphysiology [Neurons]physiology [Dendritic Spines]Cell biologyultrastructure [Dendritic Spines]metabolism [Receptor trkB]Synaptic VesiclesFilopodiaultrastructure [Synaptosomes]Disks Large Homolog 4 ProteinMicrotubule-Associated ProteinsCognitive NeuroscienceDendritic Spinesmetabolism [Disks Large Homolog 4 Protein]Nerve Tissue Proteinsgenetics [Receptor trkB]03 medical and health sciencesCellular and Molecular NeuroscienceOrgan Culture Techniquesphysiology [Synaptic Vesicles]metabolism [Vesicular Glutamate Transport Protein 1]TrkB protein ratdrug effects [Synaptic Potentials]Synaptic vesicle recyclingAnimalsHumansReceptor trkBddc:610metabolism [Synaptosomes]metabolism [Nerve Tissue Proteins]Viaat protein ratBrain-Derived Neurotrophic Factormetabolism [Microtubule-Associated Proteins]Rats030104 developmental biologygenetics [Synaptic Potentials]nervous systemcytology [Hippocampus]Synaptic plasticityultrastructure [Synapses]SynapsesVesicular Glutamate Transport Protein 1CPNE6 protein ratphysiology [Synapses]Carrier Proteins030217 neurology & neurosurgerymetabolism [Carrier Proteins]SynaptosomesCerebral cortex (New York, N.Y. : 1991)
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An evolutionary perspective on the role of mesencephalic astrocyte-derived neurotrophic factor (MANF): At the crossroads of poriferan innate immune a…

2017

The mesencephalic astrocyte-derived neurotrophic factor (MANF) belongs to a recently discovered family of neurotrophic factors. MANF can be secreted but is generally resident within the endoplasmic reticulum (ER) in neuronal and non-neuronal cells, where it is involved in the ER stress response with pro-survival effects. Here we report the discovery of the MANF homolog SDMANF in the sponge Suberites domuncula. The basal positioning of sponges (phylum Porifera) in the animal tree of life offers a unique vantage point on the early evolution of the metazoan-specific genetic toolkit and molecular pathways. Since sponges lack a conventional nervous system, SDMANF presents an enticing opportunity…

0301 basic medicineEvolutionBiophysicsApoptosisBiologyBiochemistrylcsh:Biochemistry03 medical and health sciencesNeurotrophic factorslcsh:QD415-436lcsh:QH301-705.5MANFInnate immunityInnate immune systemEndoplasmic reticulumbiology.organism_classificationTransport inhibitorCell biologyPoriferaSuberites domuncula030104 developmental biologylcsh:Biology (General)Unfolded protein responsebiology.proteinER stressNeurotrophinSuberitesResearch ArticleBiochemistry and Biophysics Reports
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ESC-Derived BDNF-Overexpressing Neural Progenitors Differentially Promote Recovery in Huntington's Disease Models by Enhanced Striatal Differentiation

2016

Summary Huntington's disease (HD) is characterized by fatal motoric failures induced by loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport of the neurotrophin BDNF (brain-derived neurotrophic factor). By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as a potential HD therapy approach. Transplantation of purified neural progenitors was analyzed in a quinolinic acid (QA) chemical and two genetic HD mouse models (R6/2 and N171-82Q) on the basis of distinct behavioral parameters, including CatWalk gait analysis. Explicit rescue of motor function by…

0301 basic medicineGene ExpressionBiochemistrychemistry.chemical_compoundMice0302 clinical medicineNeural Stem CellsNeurotrophic factorsGenes Reporterlcsh:QH301-705.5Neuronslcsh:R5-920NeurogenesisCell DifferentiationAnatomyembryonic stem cellsHuntington Diseaselcsh:Medicine (General)NeurogliaLocomotionNeurotrophinHuntington’s diseaseCell SurvivalBiologyMedium spiny neuronArticle03 medical and health sciencesHuntington's diseaseGeneticsmedicinestriatal differentiationAnimalsBrain-derived neurotrophic factorBrain-Derived Neurotrophic FactorCell Biologymedicine.diseaseCorpus StriatumTransplantationDisease Models Animal030104 developmental biologylcsh:Biology (General)chemistrynervous systembiology.proteinNeuroscience030217 neurology & neurosurgeryBiomarkersDevelopmental BiologyQuinolinic acidStem Cell TransplantationStem Cell Reports
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Homeostatic interplay between electrical activity and neuronal apoptosis in the developing neocortex

2017

An intriguing feature of nervous system development in most animal species is that the initial number of generated neurons is higher than the number of neurons incorporated into mature circuits. A substantial portion of neurons is indeed eliminated via apoptosis during a short time window - in rodents the first two postnatal weeks. While it is well established that neurotrophic factors play a central role in controlling neuronal survival and apoptosis in the peripheral nervous system (PNS), the situation is less clear in the central nervous system (CNS). In postnatal rodent neocortex, the peak of apoptosis coincides with the occurrence of spontaneous, synchronous activity patterns. In this …

0301 basic medicineNervous systemCentral nervous systemApoptosisNeocortexBiologyMembrane Potentials03 medical and health sciences0302 clinical medicineNeurotrophic factorsmedicineAnimalsHumansNeuronsNeocortexGeneral Neuroscience030104 developmental biologymedicine.anatomical_structurenervous systemApoptosisCerebral cortexPeripheral nervous systemSynapsesCalciumNeuroscience030217 neurology & neurosurgeryHomeostasisNeuroscience
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Imaging correlates of behavioral impairments: An experimental PET study in the rat pilocarpine epilepsy model

2018

Abstract Psychiatric comorbidities are prevalent in patients with epilepsy and greatly contribute to the overall burden of disease. The availability of reliable biomarkers to diagnose epilepsy-associated comorbidities would allow for effective treatment and improved disease management. Due to their non-invasive nature, molecular imaging techniques such as positron emission tomography (PET) are ideal tools to measure pathologic changes. In the current study we investigated the potential of [18F]fluoro-2-deoxy- d -glucose ([18F]FDG) and 2′-methoxyphenyl-(N-2′-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine ([18F]MPPF) as imaging correlates of neurobehavioral comorbidities in the pilocarpine …

0301 basic medicineOncologymedicine.medical_specialtyNeurologyEpileptogenesislcsh:RC321-571Rats Sprague-Dawley03 medical and health sciencesEpilepsychemistry.chemical_compound0302 clinical medicineNeurotrophic factorsInternal medicineMedicineAnimalsInterpersonal RelationsAnimal modellcsh:Neurosciences. Biological psychiatry. NeuropsychiatryBehaviorEpilepsymedicine.diagnostic_testbusiness.industryMental DisordersPilocarpinemedicine.diseaseRatsDisease Models Animal030104 developmental biologyBDNFPETchemistryNeurologyPositron emission tomographyPilocarpinePositron-Emission TomographyReceptor Serotonin 5-HT1ABiomarker (medicine)Female[18F]MPPFMPPF[18F]FDGbusiness030217 neurology & neurosurgerymedicine.drug
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Identification of neuronal and angiogenic growth factors in an in vitro blood-brain barrier model system: Relevance in barrier integrity and tight ju…

2016

We previously demonstrated that the co-cultivation of endothelial cells with neural cells resulted in an improved integrity of the in vitro blood-brain barrier (BBB), and that this model could be useful to evaluate the transport properties of potential central nervous system disease drugs through the microvascular brain endothelial. In this study we have used real-time PCR, fluorescent microscopy, protein arrays and enzyme-linked immunosorbent assays to determine which neural- and endothelial cell-derived factors are produced in the co-culture and improve the integrity of the BBB. In addition, a further improvement of the BBB integrity was achieved by adjusting serum concentrations and grow…

0301 basic medicineSus scrofaCell Culture TechniquesCell CommunicationBiologyMatrix metalloproteinaseBlood–brain barrierBiochemistryTight JunctionsCapillary Permeability03 medical and health sciences0302 clinical medicinePEDFIn vivoNeurotrophic factorsCell Line TumormedicineElectric ImpedanceAnimalsHumansNerve Growth FactorsAngiogenic ProteinsNeuronsTight Junction ProteinsTight junctionEndothelial CellsCell BiologyCoculture TechniquesCell biologyVascular endothelial growth factor B030104 developmental biologymedicine.anatomical_structurePhenotypeBlood-Brain BarrierImmunologyNeurovascular CouplingEndostatinCardiology and Cardiovascular Medicine030217 neurology & neurosurgerySignal TransductionMicrovascular research
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