TSPO and Neuroinflammation in Alzheimer's Disease

TSPO 和阿尔茨海默氏病的神经炎症

基本信息

  • 批准号:
    10505310
  • 负责人:
  • 金额:
    $ 36.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-01 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

Administrative Supplement Summary/Abstract: Alzheimer's disease (AD) is the most common form of dementia and one of the leading causes of morbidity and mortality worldwide. AD has a profound economic and social burden impacting the well-being of individuals, families, and a significant percentage of the world's population. It is one of the most pressing problems facing public health today. Thus, there is urgency to understand disease mechanisms to develop novel therapeutic strategies to combat this devastating disease. Neuroinflammation in the form of microglia activation and oxidative stress are hallmark features of AD. Our laboratory has had a long-standing history in the validation and application of Translocator Protein 18 kDa (TSPO) as a biomarker of neuroinflammation. TSPO is expressed in microglia and our work (in the parent grant) is focused in understanding the function(s) of TSPO in microglia. We have discovered an association between TSPO and NADPH Oxidase (NOX2) in microglia suggesting that TSPO may modulate NOX2 subunit(s) gene expression altering reactive oxygen species (ROS) production and oxidative stress in the brain. TSPO levels and NOX2 activity are both significantly increased in the brains of AD subjects and in animal models of AD. Since they are both highly expressed in AD-associated microglia, their interaction may be important in ROS production and oxidative stress leading to the aggregation of β-amyloid, neuronal loss, and cognitive deficits. We hypothesize that disruption of the TSPO-NOX2 interaction in microglia may arrest AD progression. Our working hypothesis is that 5XFAD mice (animal model of AD) that are deficient in TSPO will have a lower level of AD pathology and cognitive function deficits when compared to sex- and age-matched 5XFAD mice that are wildtype for TSPO. To this goal, in specific aim 1, we propose to use 5XFAD mice and our global TSPO knockout mice to generate 5XFAD mice with different levels of TSPO gene expression. We propose to generate 5XFAD mice that are wiltype, heterozygous, and deficient for TSPO. The goal of specific aim 2 is to use these mice to obtain preliminary data on the impact of TSPO gene dosage on the cognitive function deficits and hallmark AD pathology in 5XFAD mice. We will use the Barnes maze (spatial learning task) as one measure of cognitive function and will assess β-amyloid plaque load, and microglia and astrocyte activation using immunohistochemistry methods. The proposed studies resulting from this administrative supplement will leverage the ongoing studies in the parent grant on the association of TSPO and NOX2 in microglia and will extend them to their potential role in the neuroinflammation and neurodegeneration associated with AD. The data generated will serve to provide preliminary evidence for a larger and more comprehensive NIH proposal on the role of TSPO and NOX2 in the initiation and progression of the hallmark pathology and cognitive deficits in AD using a life course approach.
摘要/摘要:阿尔茨海默病(AD)是老年痴呆症最常见的形式

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Tomas R Guilarte其他文献

657 EFFECTS OF TPN ON INTESTINAL DEVELOPMENT
  • DOI:
    10.1203/00006450-198504000-00687
  • 发表时间:
    1985-04-01
  • 期刊:
  • 影响因子:
    3.100
  • 作者:
    Robert M Goldstein;David L Dudgeon;Gordon L Luk;Fowzia Tagi;Frank A Franklin;Tomas R Guilarte;Paul W Niemiec
  • 通讯作者:
    Paul W Niemiec

Tomas R Guilarte的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Tomas R Guilarte', 18)}}的其他基金

Peripheral BDZ Receptor - Biomarker of Neurotoxicity
外周 BDZ 受体 - 神经毒性生物标志物
  • 批准号:
    10020410
  • 财政年份:
    2019
  • 资助金额:
    $ 36.88万
  • 项目类别:
Peripheral BDZ Receptor - Biomarker of Neurotoxicity
外周 BDZ 受体 - 神经毒性生物标志物
  • 批准号:
    10176485
  • 财政年份:
    2019
  • 资助金额:
    $ 36.88万
  • 项目类别:
Peripheral BDZ Receptor - Biomarker of Neurotoxicity
外周 BDZ 受体 - 神经毒性生物标志物
  • 批准号:
    10414054
  • 财政年份:
    2019
  • 资助金额:
    $ 36.88万
  • 项目类别:
Peripheral BDZ Receptor - Biomarker of Neurotoxicity
外周 BDZ 受体 - 神经毒性生物标志物
  • 批准号:
    10622558
  • 财政年份:
    2019
  • 资助金额:
    $ 36.88万
  • 项目类别:
Peripheral BDZ Receptor - Biomarker of Neurotoxicity
外周 BDZ 受体 - 神经毒性生物标志物
  • 批准号:
    9817320
  • 财政年份:
    2019
  • 资助金额:
    $ 36.88万
  • 项目类别:
Cholinergic Neuron Degeneration in Mn Neurotoxicity
锰神经毒性中的胆碱能神经元变性
  • 批准号:
    9906056
  • 财政年份:
    2018
  • 资助金额:
    $ 36.88万
  • 项目类别:
RCMI Recruitment Core
RCMI 招聘核心
  • 批准号:
    10194589
  • 财政年份:
    2017
  • 资助金额:
    $ 36.88万
  • 项目类别:
RCMI Recruitment Core
RCMI 招聘核心
  • 批准号:
    10194596
  • 财政年份:
    2017
  • 资助金额:
    $ 36.88万
  • 项目类别:
Presynaptic Mechanisms of Lead Neurotoxicity
铅神经毒性的突触前机制
  • 批准号:
    8292734
  • 财政年份:
    2012
  • 资助金额:
    $ 36.88万
  • 项目类别:
Presynaptic Mechanisms of Lead Neurotoxicity
铅神经毒性的突触前机制
  • 批准号:
    9024526
  • 财政年份:
    2012
  • 资助金额:
    $ 36.88万
  • 项目类别:

相似国自然基金

靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    0 万元
  • 项目类别:
    面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
  • 批准号:
    2023JJ50274
  • 批准年份:
    2023
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    33 万元
  • 项目类别:
    地区科学基金项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
  • 批准号:
    n/a
  • 批准年份:
    2022
  • 资助金额:
    10.0 万元
  • 项目类别:
    省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
  • 批准号:
    81973577
  • 批准年份:
    2019
  • 资助金额:
    55.0 万元
  • 项目类别:
    面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
  • 批准号:
    81602908
  • 批准年份:
    2016
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
  • 批准号:
    81501928
  • 批准年份:
    2015
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341426
  • 财政年份:
    2024
  • 资助金额:
    $ 36.88万
  • 项目类别:
    Continuing Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341424
  • 财政年份:
    2024
  • 资助金额:
    $ 36.88万
  • 项目类别:
    Continuing Grant
PROTEMO: Emotional Dynamics Of Protective Policies In An Age Of Insecurity
PROTEMO:不安全时代保护政​​策的情绪动态
  • 批准号:
    10108433
  • 财政年份:
    2024
  • 资助金额:
    $ 36.88万
  • 项目类别:
    EU-Funded
The role of dietary and blood proteins in the prevention and development of major age-related diseases
膳食和血液蛋白在预防和发展主要与年龄相关的疾病中的作用
  • 批准号:
    MR/X032809/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.88万
  • 项目类别:
    Fellowship
Atomic Anxiety in the New Nuclear Age: How Can Arms Control and Disarmament Reduce the Risk of Nuclear War?
新核时代的原子焦虑:军控与裁军如何降低核战争风险?
  • 批准号:
    MR/X034690/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.88万
  • 项目类别:
    Fellowship
Walkability and health-related quality of life in Age-Friendly Cities (AFCs) across Japan and the Asia-Pacific
日本和亚太地区老年友好城市 (AFC) 的步行适宜性和与健康相关的生活质量
  • 批准号:
    24K13490
  • 财政年份:
    2024
  • 资助金额:
    $ 36.88万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Discovering the (R)Evolution of EurAsian Steppe Metallurgy: Social and environmental impact of the Bronze Age steppes metal-driven economy
发现欧亚草原冶金的(R)演变:青铜时代草原金属驱动型经济的社会和环境影响
  • 批准号:
    EP/Z00022X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.88万
  • 项目类别:
    Research Grant
ICF: Neutrophils and cellular senescence: A vicious circle promoting age-related disease.
ICF:中性粒细胞和细胞衰老:促进与年龄相关疾病的恶性循环。
  • 批准号:
    MR/Y003365/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.88万
  • 项目类别:
    Research Grant
Doctoral Dissertation Research: Effects of age of acquisition in emerging sign languages
博士论文研究:新兴手语习得年龄的影响
  • 批准号:
    2335955
  • 财政年份:
    2024
  • 资助金额:
    $ 36.88万
  • 项目类别:
    Standard Grant
Shaping Competition in the Digital Age (SCiDA) - Principles, tools and institutions of digital regulation in the UK, Germany and the EU
塑造数字时代的竞争 (SCiDA) - 英国、德国和欧盟的数字监管原则、工具和机构
  • 批准号:
    AH/Y007549/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.88万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了