Regulation of neuronal survival by gamma protocadherins
Regulation of neuronal survival by gamma protocadherins
批准号:
8445778
负责人:
XIAOZHONG ALEC WANG
金额:
$23.18万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2012
资助国家:
美国
项目状态:
已结题
起止时间:
2012-09-15 至 2014-08-31
关键词:
AcuteAdaptor Signaling ProteinAdultAffectAllelesAlzheimer&aposs DiseaseApoptosisApoptoticAttenuatedBindingCavernous MalformationCell surfaceCellsCerebral IschemiaCerebrumCessation of lifeChickensChronicCytoplasmic TailDataDevelopmentDominant-Negative MutationEctopic ExpressionEnsureExperimental ModelsFamilyGeneticHumanIn VitroIndividualInterneuronsInvestigationKnockout MiceMAP Kinase GeneMAPK14 geneMediatingMembraneMitochondriaModelingMolecularMusMutationNatureNerve DegenerationNervous system structureNeurodegenerative DisordersNeuronsPathogenesisPathway interactionsPhosphorylationPlayPopulationProcessProtein IsoformsProteinsReactive Oxygen SpeciesRegulationRetinal Ganglion CellsRoleShapesSignal PathwaySignal TransductionSpinalSpinal CordStrokeSynapsesTestingWorkattenuationexcitotoxicityin vivoin vivo Modelmouse modelnervous system developmentneurodevelopmentneuron apoptosisneuronal cell bodyneuronal survivalneurotrophic factorpostsynapticpresynapticprotein aggregateprotein complexprotein protein interactionresearch studyspinal pathway
中文摘要
描述(由申请人提供):神经元死亡不仅对形成发育中的神经系统的大小和连通性至关重要,而且对神经退行性疾病和中风的发病也有重要作用。越来越多的遗传学证据表明,簇状原钙粘蛋白(Pcdhs)在神经元存活调控中起着重要作用。我们的初步数据显示,PDCD10,也称为CCM3,是人类脑海绵状血管瘤的一种致病遗传缺陷,作用于Pcdh-?S作为这个函数的中介。为了更好地理解Pcdhs调节神经元存活的分子途径,我们将利用转基因小鼠模型,通过评估PDCD10蛋白相互作用网络中单个组分的作用,来定义PDCD10下游的分子途径。
英文摘要
DESCRIPTION (provided by applicant): Neuronal death is not only essential in shaping the size and connectivity of the developing nervous system, but also contributes significantly to the pathogenesis of neurodegenerative diseases and stroke. Accumulating genetic evidence shows that clustered protocadherins (Pcdhs) play an important role in the regulation of neuronal survival. Our preliminary data show that PDCD10, also known as CCM3, a causative genetic defect for Cerebral Cavernous Malformations in human, acts downstream of Pcdh-?s to mediate this function. To better understand molecular pathways by which Pcdhs regulate neuronal survival, we will define the molecular pathways downstream of PDCD10 by evaluating the role of individual components in PDCD10 protein interaction network using genetically modified mouse models.
PUBLIC HEALTH RELEVANCE: Developmental neuronal death ensures the appropriate size and connectivity of the nervous system and aberrant neuronal death in adulthood is commonly associated with chronic neurodegenerative diseases such as Alzheimer's disease, and acute cerebral ischaemia/stroke. The objective of this project is to elucidate how neurons signal through a large family of cell surface molecules-protocadherins to regulate neuronal survival during normal development and how misregulation of this pathway leads to neurodegeneration.
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