Deciphering the role of junctional adhesion molecule-A in neutrophil-driven inflammatory response in Alzheimer disease
解读连接粘附分子-A 在阿尔茨海默病中性粒细胞驱动的炎症反应中的作用
基本信息
- 批准号:10752753
- 负责人:
- 金额:$ 65.85万
- 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:2023-08-15 至 2028-04-01
- 项目状态:未结题
- 来源:
- 关键词:3xTg-AD mouseAcuteAddressAdverse effectsAffectAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease modelAmyloid beta-Protein PrecursorAnti-Inflammatory AgentsAttenuatedAutoimmune DiseasesAutomobile DrivingB-LymphocytesBehavioralBloodBlood PlateletsBlood VesselsBrainCXCL1 geneCell RespirationCellsCerebral Amyloid AngiopathyCerebrovascular systemChronicCognitive deficitsComplexDataDepositionDevelopmentDiseaseDisease ProgressionElementsEncephalitisEndotheliumEnvironmental Risk FactorEventExtravasationFoundationsGenesGeneticHemostatic AgentsImmuneImmune responseImpaired cognitionInflammationInflammation MediatorsInflammatoryInflammatory ResponseInjuryInnate Immune ResponseInvadedIronKnock-outKnockout MiceLearningLeukocyte Adhesion MoleculesLeukocytesMacrophageMembraneMemoryMemory LossMicrogliaMitochondriaModalityMolecularMusMutationNerve DegenerationNeurodegenerative DisordersNeurofibrillary TanglesNeutrophil ActivationNeutrophil InfiltrationOxidative StressPathogenesisPathologicPathologyPeptidesPeripheralPhenotypePlayProcessProteinsProteomicsRegulationRoleSenile PlaquesSerumSideSynapsesSystemTFF1 geneTestingTight JunctionsTransgenic OrganismsVascular Diseasesantagonistbehavioral outcomeblood vessel occlusionbrain endothelial cellbrain parenchymacerebrovascularcytokinedefined contributiondesignextracellulargenetic manipulationhyperphosphorylated tauimprovedjunctional adhesion moleculemigrationmonocytemouse modelneurodegenerative dementianeuroinflammationneuron lossneuropathologyneutrophilnovel therapeutic interventionnovel therapeuticspathogenperipheral bloodpresenilin-1preventrecruittau Proteinstranscriptomicstreatment strategyvascular injury
项目摘要
Accumulating evidence suggests that Alzheimer’s disease (AD)-related inflammation
progresses in two different but interrelated compartments: the blood and the brain,
implying that leukocytes could lead to “brain activation,” while brain inflammation may
impact the peripheral system by inflammatory mediators. AD has predominantly chronic
neuroinflammation components that drive neurodegeneration and cerebrovascular
inflammation. However, recent studies have revealed that factors involved in acute
inflammatory response, neutrophils, contribute to pathology and cognitive impairment in
AD. Why and how neutrophils “invade” the AD-affected brain and contribute to ongoing
neurodegeneration is still largely unknown. The proposed study is designed to elucidate
critical cellular and molecular events regulating brain endothelial cell-neutrophil interaction
that can lead to neutrophil recruitment and occlusion of blood vessels and neutrophil
driven exacerbation of inflammatory processes in AD. Our preliminary data indicate that
junctional adhesion molecule-A (JAM-A), a tight junction molecule that in inflammation
acts as a leukocyte adhesion molecule, is upregulated at the brain endothelium in AD.
Genetic manipulation of JAM-A as well as a specifically designed JAM-A antagonist
peptide reduced neutrophil infiltration and neutrophil extracellular traps (NETs) formation
in brain blood vessels and parenchyma and reduced behavioral deficits in a mouse AD
model. This proposal, therefore, highlights how JAM-A drives neutrophil-dependent
inflammatory responses in AD and specifically addresses the hypothesis that, “JAM-A
plays critical roles in neutrophil recruitment and NETs formation driving the
inflammatory and vascular injury in AD conditions”. Specifically, it will evaluate: a)
how a global JAM-A knockout affects vascular and parenchymal neutrophil accumulation
and behavioral outcomes in AD, b) the impact of endothelial-associated JAM-A on
vascular and parenchymal neutrophil accumulation and behavioral outcomes in AD, c) the
cellular and molecular mechanisms underlying the adverse effects of JAM-A in AD and d)
the effects of JAM-A antagonist peptides on AD-induced neutrophil accumulation and
behavioral deficits. Collectively, these studies will provide new information related to the
mechanisms of neutrophil accumulation and NETs occurrence that is relevant not only to
AD but also to multiple disease states. Hopefully, this will help to elucidate novel
therapeutic strategies for treatment of AD-associated inflammation.
越来越多的证据表明阿尔茨海默病(AD)相关的炎症
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 }}
ANUSKA V. ANDJELKOVIC-ZOCHOWSKA其他文献
ANUSKA V. ANDJELKOVIC-ZOCHOWSKA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('ANUSKA V. ANDJELKOVIC-ZOCHOWSKA', 18)}}的其他基金
Molecular mechanism mediating apicobasal brain endothelial cells polarity in cerebral cavernous malformation type 3-lesion
脑海绵状血管瘤3型病变中顶基底层脑内皮细胞极性的分子机制
- 批准号:
10526456 - 财政年份:2022
- 资助金额:
$ 65.85万 - 项目类别:
The mechanism of blood brain barrier impairment in cerebral cavernous malformatio
脑海绵状血管瘤血脑屏障损伤的机制
- 批准号:
8166264 - 财政年份:2011
- 资助金额:
$ 65.85万 - 项目类别:
The mechanism of blood brain barrier impairment in cerebral cavernous malformatio
脑海绵状血管瘤血脑屏障损伤的机制
- 批准号:
8320860 - 财政年份:2011
- 资助金额:
$ 65.85万 - 项目类别:
Effect of nicotine on postischemic brain inflammation.
尼古丁对缺血后脑炎症的影响。
- 批准号:
7587078 - 财政年份:2008
- 资助金额:
$ 65.85万 - 项目类别:
Chemokine Effects on Blood-brain Barrier Permeability
趋化因子对血脑屏障通透性的影响
- 批准号:
6720934 - 财政年份:2003
- 资助金额:
$ 65.85万 - 项目类别:
Chemokine Effects on Blood-brain Barrier Permeability
趋化因子对血脑屏障通透性的影响
- 批准号:
6982792 - 财政年份:2003
- 资助金额:
$ 65.85万 - 项目类别:
Chemokine Effects on Blood-brain Barrier Permeability
趋化因子对血脑屏障通透性的影响
- 批准号:
6823224 - 财政年份:2003
- 资助金额:
$ 65.85万 - 项目类别:
相似海外基金
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 65.85万 - 项目类别:
Fellowship
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 65.85万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 65.85万 - 项目类别:
Collaborative R&D
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 65.85万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 65.85万 - 项目类别:
Research Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 65.85万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 65.85万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 65.85万 - 项目类别:
Standard Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 65.85万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Collaborative Research: Changes and Impact of Right Ventricle Viscoelasticity Under Acute Stress and Chronic Pulmonary Hypertension
合作研究:急性应激和慢性肺动脉高压下右心室粘弹性的变化和影响
- 批准号:
2244994 - 财政年份:2023
- 资助金额:
$ 65.85万 - 项目类别:
Standard Grant














{{item.name}}会员




