Project 3: Autophagy dysfunction and neuronal activity in FTD
项目 3:FTD 中的自噬功能障碍和神经元活动
基本信息
- 批准号:10011929
- 负责人:
- 金额:$ 31.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-30 至 2023-02-28
- 项目状态:已结题
- 来源:
- 关键词:AcetylationAddressAffectAutophagocytosisAutophagosomeAutopsyAxonBrainCell physiologyChemicalsChromosome PairingClustered Regularly Interspaced Short Palindromic RepeatsCollaborationsDataDiseaseElectrophysiology (science)EndosomesEnvironmentExcisionExperimental ModelsFailureFreezingFrontotemporal DementiaFunctional disorderGeneticHomeostasisHumanLinkMaintenanceMammalian CellMediatingMolecular ChaperonesNeurodegenerative DisordersNeuronal DysfunctionNeuronsPathogenicityPathway interactionsPatientsPost-Translational Protein ProcessingPropertyProteinsProteomeProteomicsQuality ControlReporterRouteSystemTauopathiesTestingToxic effectUp-RegulationVariantbrain tissuedata integrationextracellularinduced pluripotent stem cellintervention effectknock-downmutantneuron lossneuronal cell bodyneurotoxicityprotein degradationproteostasisregional differenceresponsetau Proteinstau aggregationtau mutationtau phosphorylationuptake
项目摘要
Project 3: Autophagy dysfunction and neuronal activity in FTD Ana Maria Cuervo
SUMMARY
This proposal investigates the interplay between pathogenic forms of tau and selective forms of autophagy in
the context of frontotemporal dementia (FTD). We will coordinate the activities of this project with those of
Project 1 and Project 2 to test our working hypothesis that tau-mediated toxicity in the autophagic pathways
underlie the basis for the altered tau proteostasis and functional alterations observed in FTD-affected neurons.
Project 3 will use cutting edge proteomics (MS Core) and genetics (CRISPR Core) in iPSC-derived neurons to
investigate: 1) effect of pathogenic intra- and extracellular tau in the activity of three different forms of selective
autophagy; 2) consequences of blockage of each of these forms of autophagy on neuronal activity and tau
uptake. Project 3 will also utilize postmortem frozen human brain tissue from controls and FTD-tau patients
(Human Core) to identify 3) changes in the properties of tau associated with autophagic compartments in
control and patient brains. Assisted by the CRISPR Core, we will modulate levels of differentially tau-
interacting proteins and address the effect of this intervention on autophagy and neuronal activity.
Integration of data (Data Core) generated by this project with that from the other two projects in the Center will
allow us to elucidate the contribution of tau toxicity on the autophagic system to the neuronal activity imbalance
observed in FTD.
项目3:FTD Ana Maria Cuervo中的自噬功能障碍和神经元活性
总结
该提案调查了tau蛋白的致病形式和自噬的选择性形式之间的相互作用,
额颞叶痴呆(FTD)我们将协调这一项目的活动与
项目1和项目2来检验我们的工作假设,即自噬途径中的tau介导的毒性
是在FTD影响的神经元中观察到的tau蛋白稳态改变和功能改变的基础。
项目3将在iPSC衍生的神经元中使用尖端蛋白质组学(MS Core)和遗传学(CRISPR Core),
研究:1)致病性胞内和胞外tau蛋白在三种不同形式的选择性
自噬; 2)阻断这些形式的自噬中的每一种对神经元活性和tau蛋白的影响
摄取。项目3还将利用来自对照组和FTD-tau患者的死后冷冻人脑组织
(人类核心),以确定3)与自噬区室相关的tau性质的变化,
控制和病人的大脑。在CRISPR核心的帮助下,我们将调节不同的tau蛋白水平,
相互作用的蛋白质,并解决这种干预对自噬和神经元活性的影响。
将本项目产生的数据(数据核心)与中心其他两个项目产生的数据进行整合,
使我们能够阐明tau蛋白对自噬系统的毒性对神经元活性失衡的贡献
在FTD中观察到。
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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ANA MARIA CUERVO其他文献
ANA MARIA CUERVO的其他文献
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{{ truncateString('ANA MARIA CUERVO', 18)}}的其他基金
Molecular and Cellular Mechanisms of the Lysosomal Storage Disease Cystinosis
溶酶体贮积病胱氨酸中毒的分子和细胞机制
- 批准号:
10434057 - 财政年份:2017
- 资助金额:
$ 31.95万 - 项目类别:
Molecular and Cellular Mechanisms of the Lysosomal Storage Disease Cystinosis
溶酶体贮积病胱氨酸中毒的分子和细胞机制
- 批准号:
10683169 - 财政年份:2017
- 资助金额:
$ 31.95万 - 项目类别:
Project 3: Autophagy dysfunction and neuronal activity in FTD
项目 3:FTD 中的自噬功能障碍和神经元活动
- 批准号:
9292170 - 财政年份:2016
- 资助金额:
$ 31.95万 - 项目类别:
Understanding Alzheimer's Disease in the Context of the Aging Brain
在大脑老化的背景下了解阿尔茨海默病
- 批准号:
9856238 - 财政年份:2016
- 资助金额:
$ 31.95万 - 项目类别:
Functional Consequences of Impaired Autophagy in Aging
衰老过程中自噬受损的功能后果
- 批准号:
8792022 - 财政年份:2014
- 资助金额:
$ 31.95万 - 项目类别:
Control of vesicular trafficking in the hepatocyte.
控制肝细胞中的囊泡运输。
- 批准号:
8633455 - 财政年份:2013
- 资助金额:
$ 31.95万 - 项目类别:
Control of vesicular trafficking in the hepatocyte
肝细胞中囊泡运输的控制
- 批准号:
9888362 - 财政年份:2013
- 资助金额:
$ 31.95万 - 项目类别:
Control of vesicular trafficking in the hepatocyte.
控制肝细胞中的囊泡运输。
- 批准号:
8838778 - 财政年份:2013
- 资助金额:
$ 31.95万 - 项目类别:
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