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。
以及破坏这些活动的目标。一个令人信服的替代方法是自然地描绘
发生的保护机制。一些百岁老人在认知上仍然完好无损,尽管
极端暴露在认知障碍和AD、衰老的最强风险因素中。我们
假设这些百岁老人和他们的部分后代有保护因素
这会导致这种韧性,甚至在某些情况下,对认知能力下降的抵抗
痴呆症。在行政、表型和生物样本的支持下,以及
神经成像核心和项目1(恢复力和阻力表型),这是
《百岁老人及其后代对阿尔茨海默病的抵抗力/恢复力》(RADCO)研究致力于
发现预防认知障碍、阿尔茨海默病和其他疾病的因素和机制
痴呆症。该项目涉及三种相关方法:遗传学(目标1)、转录学
年龄相关脑病理的分析(AIM 2)和3D人类神经胶质细胞培养模型(AIM
3)。我们的目标是1)识别抗逆性/抗逆性的遗传变异和生物学机制
在百岁认知超老年人中,2)预测认知弹性的机制并验证
可以增强人脑细胞弹性/抵抗力的候选药物,以及3)建立
百岁老人诱导多能干细胞及其衍生的3D脑细胞模型
超级老人来测试这些机制,以及发现和测试其他可能被利用的机制
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:
-
资助金额:$80.62万
-
财政年份:2021
-
负责人:Doo Yeon Kim
-
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
-
批准号:10689333
-
项目类别:
-
资助金额:$102.68万
-
财政年份:2021
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负责人:Doo Yeon Kim
-
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
-
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
-
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
-
项目类别:
-
资助金额:$75.6万
-
财政年份:2019
-
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
-
财政年份:2014
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负责人:Doo Yeon Kim
-
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:
-
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
-
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
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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