Tau-seed protein interactome and its role in neurodegenerative tauopathies
Tau 种子蛋白相互作用组及其在神经退行性 tau 病中的作用
基本信息
- 批准号:10480212
- 负责人:
- 金额:$ 4.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-30 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAffinityAgeAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAutopsyBehavioralBiochemicalBioinformaticsBrainClinicalComplexData SetDiseaseDown-RegulationElectrophysiology (science)GoalsHeterogeneityHistologicHumanImageIndividualKnowledgeLinkMaintenanceMass Spectrum AnalysisMedicineMicrofluidicsMicroscopyModelingMolecularMolecular ConformationMolecular WeightMutationNatureNerve DegenerationNeurodegenerative DisordersNeurofibrillary TanglesNeuronsPathogenesisPathologicPathologyPathway AnalysisPatientsPhysiologicalPlayProcessProgressive Supranuclear PalsyPropertyProteinsProteomicsReportingResearchResolutionRisk FactorsRoleSamplingScaffolding ProteinSeedsSeriesStructureSynapsesSynaptic VesiclesSystemTauopathiesTestingTissuesWorkbasebassoon proteincytomatrixgenome wide association studyhuman modelin vivoloss of functionmonomermouse modelmutantneurotoxicitynon-dementednovelpresynapticprotein aggregationproteostasisscaffoldtau Proteinstau aggregationtau interactiontranscriptome sequencing
项目摘要
Pathological aggregation of tau and the preponderance of neurofibrillary tangles (NFT) or other inclusions
containing tau are defining histopathological features of Alzheimer's disease (AD) and many neurodegenerative
diseases collectively known as tauopathies. A major focus of research has been the understanding of the
propagation of pathological tau in AD patient brains that follow neuronal networks. Despite the knowledge
acquired, the cellular mechanism involved in tau propagation, the nature of the tau species involved in the
spreading and the precise seeding/template remains unclear. Considering the preponderant role of tau
propagation in the pathogenesis of AD and other tauopathies, we performed an unbiased quantitative Mass
Spectrometry based study to determine the specific tau species involved in the spreading and the proteins that
specifically interact with this “tau-seed”. Bassoon (BSN), a large scaffolding protein of the presynaptic active
zone, was identified as a significant interactor of the tau-pathological-seed isolated from a mouse model for
tauopathy, as well as from AD and PSP postmortem samples. Prior research in AD and PSP patient samples have
linked BSN with both tauopathies. Therefore, the main goal of this proposal is to determine and dissect the mechanism by which BSN functions as a scaffold to stabilize and facilitate the spreading and neurotoxicity of a tau-pathological-seed. By introducing a series of biochemical, molecular, histological, electrophysiological, behavioral, imaging, bioinformatics and Mass Spectrometry based strategies together with mouse model, cellular culture and human postmortem tissue, this proposal will 1. evaluate the role of BSN in tau pathogenesis in vivo, 2. determine the mechanistic base of BSN in tau aggregation, propagation and synaptotoxicity in neuronal systems and 3. test if BSN's association with tau-pathological-seed is strain specific in human brains from a diverse set of tauopathies. Gaining a better understanding of the contribution of BSN on the formation, stabilization and propagation of a pathological tau-seed is highly significant since it may provide important information that will increase our understanding on the mechanism(s) involved in tau propagation, the precise nature of the tau-seed involved in this process and its role in the neurodegeneration associated to AD and other tauopathies.
病理聚集的tau和神经原纤维缠结(NFT)或其他内含物的优势
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Cristian Lasagna-Reeves其他文献
Cristian Lasagna-Reeves的其他文献
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{{ truncateString('Cristian Lasagna-Reeves', 18)}}的其他基金
Identify and study the roles of key genes and proteins in subpopulations of Alzheimer's disease patients with uncoupled neurofibrillary tangles
识别和研究关键基因和蛋白质在具有解偶联神经原纤维缠结的阿尔茨海默病患者亚群中的作用
- 批准号:
10525012 - 财政年份:2022
- 资助金额:
$ 4.3万 - 项目类别:
Tau-seed protein interactome and its role in neurodegenerative tauopathies
Tau 种子蛋白相互作用组及其在神经退行性 tau 病中的作用
- 批准号:
10456475 - 财政年份:2021
- 资助金额:
$ 4.3万 - 项目类别:
Tau-seed protein interactome and its role in neurodegenerative tauopathies
Tau 种子蛋白相互作用组及其在神经退行性 tau 病中的作用
- 批准号:
10407715 - 财政年份:2021
- 资助金额:
$ 4.3万 - 项目类别:
Tau-seed protein interactome and its role in neurodegenerative tauopathies
Tau 种子蛋白相互作用组及其在神经退行性 tau 病中的作用
- 批准号:
10470271 - 财政年份:2020
- 资助金额:
$ 4.3万 - 项目类别:
Tau-seed protein interactome and its role in neurodegenerative tauopathies
Tau 种子蛋白相互作用组及其在神经退行性 tau 病中的作用
- 批准号:
10683165 - 财政年份:2020
- 资助金额:
$ 4.3万 - 项目类别:
Tau-seed protein interactome and its role in neurodegenerative tauopathies
Tau 种子蛋白相互作用组及其在神经退行性 tau 病中的作用
- 批准号:
10268217 - 财政年份:2020
- 资助金额:
$ 4.3万 - 项目类别:
Tau-seed protein interactome and its role in neurodegenerative tauopathies
Tau 种子蛋白相互作用组及其在神经退行性 tau 病中的作用
- 批准号:
10093443 - 财政年份:2020
- 资助金额:
$ 4.3万 - 项目类别:
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