IMPORTANCE OF PERIODONTITIS IN THE INNATE IMMUNE REGULATION OF ALZHEIMER'S DISEASE
牙周炎在阿尔茨海默病先天免疫调节中的重要性
基本信息
- 批准号:10658447
- 负责人:
- 金额:$ 37.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-01 至 2028-02-29
- 项目状态:未结题
- 来源:
- 关键词:Abeta synthesisAccelerationAdultAffectAlveolar Bone LossAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease pathologyAlzheimer&aposs disease riskAmyloid beta-ProteinBrainCellsCentral Nervous System DiseasesChronicClassical Complement PathwayClinicalCommunicable DiseasesComplementComplement 1qComplement ActivationDementiaDevelopmentDiseaseDisease ProgressionEpidemiologyEtiologyGene Expression ProfileGrantHumanImmuneImpaired cognitionImpairmentIn VitroIndividualInfectionInflammationInflammation MediatorsInflammatoryInflammatory ResponseInvadedKnowledgeLigatureLinkLiteratureMediatingMicrogliaModelingMusNatural ImmunityNerve DegenerationNeurodegenerative DisordersNeuronsOralOsteitisPathogenicityPeptide Initiation FactorsPeriodontal DiseasesPeriodontal InfectionPeriodontitisPlayPorphyromonas gingivalisPredispositionPrevalenceProcessProductionReportingResearchRoleSeveritiesSeverity of illnessSourceStimulusSynapsesTestingTimeTissuesTooth structureTrainingWild Type Mouseabeta accumulationage relatedbehavioral impairmentchronic infectioncomplement systemcytokineeffectiveness evaluationglial activationimmunoregulationin vivoinsightmicrobialmutantneuroinflammationnoveloral infectionperiodontopathogenpreventive interventionresponse
项目摘要
Project Summary/Abstract
Albeit periodontal disease is a local chronic infectious inflammatory process affecting tissues supporting teeth,
it can also have systemic consequences. Along these lines are reports that Alzheimer’s disease (AD) is
epidemiologically associated with periodontal disease. Yet, the mechanisms underlying this association are
not delineated. Our preliminary studies provide new evidence that a keystone periodontal pathogen
Porphyromonas gingivalis (Pg) could enter the brain and exacerbate amyloid-b (Ab) accumulation,
neuroinflammation, microglia activation, synapse loss, and cognitive and behavioral impairments in AD mice
upon oral gavage infection. Microglia are the primary innate immune cells in the brain, and microglial
activation is an invariable feature of AD pathology. The complement system also represents a major part of
innate immunity, and microglia have been identified as the dominant source of C1q, the initiation factor of the
classical complement pathway, in the brain. The objective of this application is to understand the importance
of periodontitis in regulating microglial in AD, and the role of complement component C1q in microglial
activation and AD progression. Based on the literature and our preliminary results, we hypothesize that
periodontal infection and inflammation not only increase the severity of AD, but also increase the risk of AD,
via potentiating Ab-primed microglial activation and sensitizing microglia for a heightened inflammatory
response to subsequent pathogenic stimuli. In addition, periodontitis-associated persistent C1q activation is
critical for microglial priming and activation, and the increased neurodegeneration in AD. We will test our
hypothesis by pursuing two specific aims. Aim 1 will determine how periodontitis regulates microglial
activation in AD using three different models of periodontitis. Aim 2 will determine the role of complement
component C1q in microglial activation and AD development following Pg infection. Our proposed studies
will provide novel and significant insights into the association between periodontal infection and AD.
Understanding how a prevalent chronic infection like periodontitis modulates complement and microglial
activation will advance our understanding of the mysterious etiology of AD. The knowledge obtained from
these studies will provide a basis for targeting microbial etiology and periodontal therapy to ameliorate the
clinical manifestations of AD and lower AD prevalence.
项目总结/摘要
虽然牙周病是一种局部慢性感染性炎症过程,
它还可能产生系统性后果。沿着这些线索有报道说阿尔茨海默病(AD)是
与牙周病流行病学相关。然而,这种关联的机制是
没有划定。我们的初步研究提供了新的证据,
牙龈卟啉单胞菌(Pg)可进入大脑并加剧淀粉样蛋白-b(Ab)积聚,
AD小鼠中的神经炎症、小胶质细胞活化、突触丢失以及认知和行为障碍
经口灌胃感染。小胶质细胞是大脑中主要的先天免疫细胞,
激活是AD病理学的不变特征。补体系统也代表了
先天免疫和小胶质细胞已被确定为C1 q的主要来源,C1 q是免疫系统的起始因子。
经典的补体途径。本申请的目的是了解
牙周炎对AD小胶质细胞的调节作用以及补体C1 q在AD小胶质细胞中的作用
激活和AD进展。根据文献和我们的初步结果,我们假设
牙周感染和炎症不仅会增加AD的严重程度,还会增加AD的风险,
通过增强Ab引发的小胶质细胞活化和使小胶质细胞对升高的炎症反应敏感,
对后续致病刺激的反应。此外,牙周炎相关的持续性C1 q激活,
对于小胶质细胞的启动和激活以及AD中神经变性的增加至关重要。我们将测试我们的
通过追求两个具体目标的假设。目的1将确定牙周炎如何调节小胶质细胞
使用三种不同的牙周炎模型研究AD中的激活。目标2将确定补体的作用
C1 q在Pg感染后小胶质细胞活化和AD发展中的作用。我们建议的研究
将为牙周感染和AD之间的关联提供新的和重要的见解。
了解牙周炎等慢性感染如何调节补体和小胶质细胞
激活将促进我们对AD神秘病因学的理解。知识来自于
这些研究将为靶向微生物病因学和牙周治疗提供基础,
降低AD患病率。
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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Ping Zhang其他文献
毛细管电泳差分非接触电导检测器测定氨基酸
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:6.1
- 作者:
Yaolong Li;Zhenli Zhang;Ping Zhang;Qi Kang - 通讯作者:
Qi Kang
Ping Zhang的其他文献
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{{ truncateString('Ping Zhang', 18)}}的其他基金
ROLE OF OSTEOCLAST PRECURSORS IN PERIODONTAL BONE LOSS
破骨细胞前体在牙周骨丢失中的作用
- 批准号:
9381236 - 财政年份:2017
- 资助金额:
$ 37.13万 - 项目类别:
ROLE OF OSTEOCLAST PRECURSORS IN PERIODONTAL BONE LOSS
破骨细胞前体在牙周骨丢失中的作用
- 批准号:
10201568 - 财政年份:2017
- 资助金额:
$ 37.13万 - 项目类别:
Molecular mechanisms of the innate regulation of osteoclastogenesis.
破骨细胞生成先天调节的分子机制。
- 批准号:
8488432 - 财政年份:2012
- 资助金额:
$ 37.13万 - 项目类别:
Molecular mechanisms of the innate regulation of osteoclastogenesis.
破骨细胞生成先天调节的分子机制。
- 批准号:
8383398 - 财政年份:2012
- 资助金额:
$ 37.13万 - 项目类别:
Structual and function of kinase signaling complexes
激酶信号复合物的结构和功能
- 批准号:
10262432 - 财政年份:
- 资助金额:
$ 37.13万 - 项目类别:
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