Environmental copper exposure and its impact on microglial Abeta clearance
环境铜暴露及其对小胶质细胞 Abeta 清除的影响
基本信息
- 批准号:8930156
- 负责人:
- 金额:$ 15.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-19 至 2016-02-29
- 项目状态:已结题
- 来源:
- 关键词:Abeta clearanceAdverse effectsAffectAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease riskAmyloid beta-ProteinAstrocytesBindingBrainCellsCessation of lifeCholesterolCholesterol HomeostasisChronicCognitionCopperDataDepositionDevelopmentDietDiseaseElderlyEnvironmentEnvironmental Risk FactorFunctional disorderGene Expression ProfileGenerationsGenesGenetic Predisposition to DiseaseGenotypeGoalsHealthHeavy MetalsHomeostasisHumanImpaired cognitionImpairmentInflammatoryLate Onset Alzheimer DiseaseLifeLinkMediatingMetal exposureMicrogliaMolecularMusNerve DegenerationNeuraxisNeurogliaNeuronsOccupationalOnset of illnessPathologyPhagocytosisPopulationProductionRNA SequencesRegulatory PathwayRiskRisk FactorsRunningSynapsesTechniquesTestingTherapeuticToxic effectabeta accumulationcell typecholesterol traffickingfunctional disabilitygenetic risk factorgenome-widegenome-wide analysishigh riskimmunoregulationin vivoinsightmind controlmouse modelneuroinflammationneuropathologyneurotoxicitynovelpreventresponsetau Proteinstranscriptome sequencing
项目摘要
DESCRIPTION (provided by applicant): Environmental and occupational copper exposure has long been considered one of the environmental risk factors for Alzheimer's disease (AD). However, the late life impact of the chronic copper (Cu) exposure and its mechanisms of action in the central nervous system (CNS) have not been fully elucidated. While its direct toxicity on neurons and interaction to amyloid-beta (Aß) species are currently been studied, its chronic impact on other non-neuronal cells in the CNS has been overlooked. We hypothesize that a chronic environmentally-relevant Cu exposure impairs the activation of microglial phagocytosis and neuroinflammatory responses, promoting a pathological buildup of Aß species, synaptic loss and cognitive decline. The objective of this study is to determine whether the copper-mediated functional impairment of glial activity promotes neurodegeneration and AD neuropathology in vivo. To achieve our goal, we propose to apply two novel techniques to determine microglia- and astrocyte-specific transcriptome dynamics following chronic Cu exposure in vivo. Our proposed project will uncover the critical pathogenic impact of Cu exposure on microglia, astrocytes and neuroinflammation, and the underlying molecular mechanism by which glial dysfunction leads to the onset and progression of AD in a temporal manner.
描述(由申请人提供):长期以来,环境和职业铜暴露一直被认为是阿尔茨海默病(AD)的环境风险因素之一。然而,慢性铜(Cu)暴露的晚年影响及其在中枢神经系统(CNS)中的作用机制尚未完全阐明。虽然目前研究了其对神经元的直接毒性和与淀粉样蛋白-β(A β)物质的相互作用,但其对CNS中其他非神经元细胞的慢性影响却被忽视了。我们假设,慢性环境相关的铜暴露损害小胶质细胞吞噬作用和神经炎症反应的激活,促进病理性积聚的AAPONS物种,突触丢失和认知能力下降。本研究的目的是确定铜介导的胶质细胞活性功能障碍是否促进体内神经退行性变和AD神经病理学。为了实现我们的目标,我们建议采用两种新的技术来确定小胶质细胞和星形胶质细胞特异性转录组动态慢性铜暴露在体内。我们提出的项目将揭示铜暴露对小胶质细胞,星形胶质细胞和神经炎症的关键致病影响,以及胶质功能障碍导致AD发病和进展的潜在分子机制。
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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Masashi Kitazawa其他文献
Masashi Kitazawa的其他文献
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{{ truncateString('Masashi Kitazawa', 18)}}的其他基金
Microglia dysregulation and SYK signaling in Alzheimer's disease
阿尔茨海默病中的小胶质细胞失调和 SYK 信号传导
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Neurotoxicity of particulate matter and its interaction with APOE in neurodegeneration
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Mechanisms of particulate matter-induced neurotoxicity and cognitive decline in mice
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9789887 - 财政年份:2018
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$ 15.9万 - 项目类别:
Environmental copper exposure and its impact on microglial Abeta clearance
环境铜暴露及其对小胶质细胞 Abeta 清除的影响
- 批准号:
8757425 - 财政年份:2014
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Pathogenic role of valosin-containing protein (VCP) in IBMPFD
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Pathogenic role of valosin-containing protein (VCP) in IBMPFD
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Pathogenic role of valosin-containing protein (VCP) in IBMPFD
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8399137 - 财政年份:2012
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Pathogenic Role of Abeta, tau and Inflammation in Inclusion Body Myositis
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