Role of GPNMB signaling in remyelination by oligodendrocyte progenitor cells
GPNMB 信号在少突胶质祖细胞髓鞘再生中的作用
基本信息
- 批准号:10431034
- 负责人:
- 金额:$ 7.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAdultAffectAstrocytesAutocrine CommunicationBioinformaticsBrainCD44 geneCSPG4 geneCell CountCell MaturationCell NucleusCellsChronicClinicalCorpus CallosumCuprizoneDataDemyelinating DiseasesDemyelinationsDietDiseaseGlycoproteinsHarvestHumanImmuneIn VitroIntegral Membrane ProteinKnock-in MouseKnock-outKnockout MiceLacZ GenesLeadLesionLongevityLoxP-flanked alleleMediatingMediator of activation proteinMicrogliaModelingMolecularMultiple SclerosisMusNeonatalNerve DegenerationNonmetastaticOligodendrogliaOutcomeParacrine CommunicationPathway interactionsPeptide HydrolasesRecombinantsRegulationRoleSignal TransductionSourceTestingaging brainaxonal degenerationcell typechronic demyelinationdosageglycoprotein NMBhuman diseasein vivoinsightnerve stem cellnoveloligodendrocyte progenitoroverexpressionperipheral bloodpreventreceptorremyelinationresponsestem cellssubventricular zonetherapeutic targettranscriptome sequencingtranscriptomics
项目摘要
ABSTRACT
Loss of oligodendrocytes gives rise to demyelination, ultimately resulting in axonal degeneration and debilitating
clinical outcomes in diseases like Multiple Sclerosis. While remyelination can prevent neurodegeneration, there
are currently no approved therapies for promoting remyelination. Thus, there is an urgent need to identify factors
that control remyelination. Oligodendrocyte progenitor cells (OPCs) in the adult brain are one of the key sources
of remyelinating oligodendrocytes. However in chronic demyelination, they are inefficient for remyelination due
to depletion and/or a block in their maturation. Using a combination of bioinformatic analysis and remyelination
studies in mice, we discovered a novel mediator of the 7*)? pathway, Gpnmb which is highly expressed along
with its receptor CD44 in response to demyelination. Gpnmb is a transmembrane protein that is cleaved by
proteases into an intracellular domain (Gpnmb-ICD) and an ectodomain (Gpnmb-ECD). While Gpnmb-ICD can
signal intrinsically by translocating to the nucleus, the released Gpnmb-ECD functions as an autocrine or
paracrine signal by interacting with CD44 receptor in the same cell or a neighboring cell respectively. In the first
aim, we will define the cell-autonomous function of Gpnmb in oligodendrocyte progenitor cells and in the second
aim, we will determine the combined effect of intrinsic and extrinsic Gpnmb signaling on OPCs following
cuprizone induced demyelination. Together, these studies will not only help elucidate the molecular mechanisms
involved in maturation of adult OPCs but may also identify therapeutic targets for promoting remyelination.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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Jayshree Samanta其他文献
Jayshree Samanta的其他文献
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{{ truncateString('Jayshree Samanta', 18)}}的其他基金
Novel Modulators of TGFß1 signaling in regulation of remyelination by neural stem cells
TGFα1 信号传导在神经干细胞髓鞘再生调节中的新型调节剂
- 批准号:
10544041 - 财政年份:2022
- 资助金额:
$ 7.78万 - 项目类别:
Novel Modulators of TGFß1 signaling in regulation of remyelination by neural stem cells
TGFα1 信号传导在神经干细胞髓鞘再生调节中的新型调节剂
- 批准号:
10366677 - 财政年份:2022
- 资助金额:
$ 7.78万 - 项目类别:
Role of GPNMB Signaling in Remyelination by Oligodendrocyte Progenitor Cells
GPNMB 信号在少突胶质祖细胞髓鞘再生中的作用
- 批准号:
10596170 - 财政年份:2022
- 资助金额:
$ 7.78万 - 项目类别:
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