Protective factors and mechanisms
Protective factors and mechanisms
批准号:
10276392
负责人:
Doo Yeon Kim
金额:
$124.04万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-09-30 至 2026-08-31
关键词:
3-DimensionalAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease pathologyAreaAstrocytesAutopsyBiologicalBloodBrainBrain PathologyBrain regionCell LineCell modelCellular AssayCentenarianCodeCognitiveDataDementiaDiseaseDrug CombinationsDrug usageExposure toGene FrequencyGenesGoalsHumanImpaired cognitionImpairmentLeadLife ExpectancyMeasuresMicroRNAsMicrogliaModelingMolecularNeurogliaNeuronsOrganoidsPathway interactionsPharmaceutical PreparationsPhenotypePrivatizationProcessProsencephalonRNA SequencesResearchResistanceRisk FactorsSerumSpousesTestingTherapeuticTissuesUntranslated RNAValidationVariantWorkabeta accumulationage relatedbasebrain cellcirculating biomarkersdrug candidateendophenotypeexomegenetic approachgenetic variantinduced pluripotent stem cellmicroRNA biomarkersneuroimagingoffspringprotective alleleprotective factorsrelating to nervous systemresiliencesextranscriptometranscriptome sequencingtranscriptomics
中文摘要
RADCO项目2摘要
许多认知障碍和痴呆症的研究都集中在疾病机制上
和破坏这些的目标。另一种令人信服的方法是自然地描绘
保护机制的出现。一些百岁老人的认知能力仍然完好无损,
极度暴露于认知障碍和AD的最强风险因素,衰老。我们
假设这些百岁老人和他们后代的某些部分具有保护因素
导致这种恢复力,或者在某些情况下,甚至抵抗认知能力下降,
痴呆在管理、表型分析和生物样品部门的支持下,
神经影像核心,和项目1(弹性和阻力表型),这第二个项目的
“百岁老人和后代对AD的抵抗力/恢复力”(RADCO)研究致力于
发现对认知障碍、AD和其他疾病的保护因素和机制
痴呆症该项目涉及三个相关的方法:遗传学(目标1),转录组学
分析(目的2)和年龄相关脑病理学的3D人类神经胶质细胞培养模型(目的
3)。我们的目标是:1)识别遗传变异和弹性/抗性的生物学机制
在百岁认知超级老人中,2)预测认知弹性的机制,并验证
可以增强人脑细胞的弹性/抵抗力的候选药物,以及3)建立
百岁老人的诱导多能干细胞(iPSC)和iPSC衍生的3D脑细胞模型
超级老人测试这些机制,以及发现和测试其他可能被利用
用于保护性治疗。
英文摘要
RADCO Project 2 Summary
Much of cognitive impairment and dementia research has concentrated on disease mechanisms
and targets for disrupting these. A compelling alternative approach is to delineate naturally
occurring mechanisms of protection. Some centenarians remain cognitively intact despite an
extreme exposure to the strongest risk factor for cognitive impairment and AD, aging. We
hypothesize that these centenarians and some portion of their offspring have protective factors
that lead to such resilience or in some cases, even resistance against cognitive decline and
dementia. With the support of the Administrative, Phenotyping and Biosamples, and
Neuroimaging Cores, and Project 1 (Resilience and Resistance Phenotypes), this 2nd project of
the “Resistance/Resilience to AD in Centenarians and Offspring" (RADCO) study strives to
discover factors and mechanisms protective against cognitive impairment, AD and other
dementias. This project entails three related approaches: genetics (Aim 1), transcriptomic
analyses (Aim 2), and 3D human neural-glial culture models of age-related brain pathology (Aim
3). Our goals are to 1) identify genetic variants and biological mechanisms of resilience/resistance
in centenarian cognitive superagers, 2) predict mechanisms of cognitive resilience and validate
candidate drugs that can enhance the resilience/resistance in human brain cells, and 3) establish
induced pluripotent stem cells (iPSCs) and iPSC-derived 3D brain cell models of the centenarian
superagers to test those mechanisms as well as discover and test others that could be exploitable
for protective therapeutics.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Systematic modeling and prediction of cell-type-specific and spatiotemporal crosstalk pathways in Alzheimer's Disease
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批准号:10184718
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项目类别:
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资助金额:$80.62万
-
财政年份:2021
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负责人:Doo Yeon Kim
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依托单位:
Systematic modeling and prediction of cell-type-specific and spatiotemporal crosstalk pathways in Alzheimer's Disease
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批准号:10404073
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项目类别:
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资助金额:$79.08万
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财政年份:2021
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负责人:Doo Yeon Kim
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依托单位:
Protective factors and mechanisms
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批准号:10689333
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项目类别:
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资助金额:$102.68万
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财政年份:2021
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负责人:Doo Yeon Kim
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依托单位:
Systematic modeling and prediction of cell-type-specific and spatiotemporal crosstalk pathways in Alzheimer's Disease
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批准号:10629214
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项目类别:
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资助金额:$79.08万
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财政年份:2021
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负责人:Doo Yeon Kim
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依托单位:
The impact of AD-associated genetic variants in 3D human mixed neural-glial models of AD
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批准号:10399510
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项目类别:
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资助金额:$75.6万
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财政年份:2019
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负责人:Doo Yeon Kim
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依托单位:
The impact of AD-associated genetic variants in 3D human mixed neural-glial models of AD
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批准号:10153618
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项目类别:
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资助金额:$75.6万
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财政年份:2019
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负责人:Doo Yeon Kim
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依托单位:
The impact of AD-associated genetic variants in 3D human mixed neural-glial models of AD
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批准号:10630090
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项目类别:
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资助金额:$75.6万
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财政年份:2019
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负责人:Doo Yeon Kim
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依托单位:
A novel human 3D neural cell culture system for the characterization of AD genes
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批准号:8758242
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项目类别:
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资助金额:$211.95万
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财政年份:2014
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负责人:Doo Yeon Kim
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依托单位:
Altered sodium channel metabolism in Alzheimer's disease
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批准号:7672234
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项目类别:
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资助金额:$18.77万
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财政年份:2008
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负责人:Doo Yeon Kim
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依托单位:
Altered sodium channel metabolism in Alzheimer's disease
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批准号:7532109
-
项目类别:
-
资助金额:$22.42万
-
财政年份:2008
-
负责人:Doo Yeon Kim
-
依托单位:
Alzheimer's BACE1 inhibition regulates neuronal contactin function
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批准号:9214291
-
项目类别:
-
资助金额:$34.82万
-
财政年份:1997
-
负责人:Doo Yeon Kim
-
依托单位:
Alzheimer's BACE1 inhibition regulates neuronal contactin function
-
批准号:8694311
-
项目类别:
-
资助金额:$34.82万
-
财政年份:1997
-
负责人:Doo Yeon Kim
-
依托单位:
海外基金