Mechanistic basis of inflammation in Alzheimers Disease
Mechanistic basis of inflammation in Alzheimers Disease
批准号:
10259772
负责人:
Amal O Amer
金额:
$18.47万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-09-15 至 2022-04-30
关键词:
Alzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease patientAlzheimer&aposs disease riskAmyloidAmyloid beta-ProteinAntisense OligonucleotidesAreaBrainCASP1 geneCASP4 geneCaspaseCellsCerebrospinal FluidComplexConfusionCytoskeletonDeteriorationExhibitsGene ProteinsGenetic VariationGrantHomologous GeneHousekeeping GeneHumanImmuneImpaired cognitionIn VitroIndividualInfectionInflammasomeInflammationInflammatoryInflammatory ResponseInterleukin-1 betaLabelLipopolysaccharidesLobeMediatingMemoryMicrogliaMusNeuraxisNeurodegenerative DisordersPatientsPreventionProductionPromoter RegionsProtein PrecursorsReportingReverse Transcriptase Polymerase Chain ReactionRoleSamplingSynaptic plasticityTestingUnited States National Institutes of HealthWild Type Mousebiobankbisulfite sequencingbrain tissuecytokinegenome wide methylationhigh riskin vivoinsightlearning abilitymemberoverexpressionpreventreceptor functionresponserisk variant
中文摘要
摘要
阿尔茨海默病(AD)是一种进行性炎症性神经退行性疾病,导致衰弱
认知功能障碍,仍然没有治愈或有效的预防选择。多项研究表明
大脑中的低级别炎症与较高的AD风险相关。阿尔茨海默病患者表现为
促炎细胞因子IL-1β(IL-1β)在脑脊液和脑中的过度产生
组织。重要的是,夸大的IL-1β水平有力地抑制了对正常至关重要的突触可塑性机制
记忆功能。在本申请中,我们将确定规范成员和非规范成员的功能
典型炎症体与阿尔茨海默病的关系。
英文摘要
Abstract
Alzheimer’s disease (AD) is a progressive inflammatory neurodegenerative disorder leading to debilitating
cognitive dysfunction, and is still without cure or effective prevention options. Several studies demonstrated
that low grade inflammation in the brain is associated with higher risk of AD. Patients with AD exhibit an
overproduction of the pro-inflammatory cytokine interleukin-1 beta (IL-1β) in the cerebrospinal fluid and brain
tissue. Importantly, exaggerated IL-1β levels robustly inhibit synaptic plasticity mechanisms critical for normal
memory function. In this application we will determine the function of members of the canonical and non-
canonical inflammasome in relation of AD.
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