Brain Pericyte and Amyloid-beta Peptide Interaction
脑周细胞和淀粉样蛋白-β 肽相互作用
基本信息
- 批准号:8337907
- 负责人:
- 金额:$ 14.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-01 至 2015-08-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAdhesionsAffectAlzheimer&aposs DiseaseAmyloidAmyloid beta-ProteinAngiopoietin-1Biological PreservationBlood - brain barrier anatomyBlood VesselsBlood capillariesBrainCell ShapeCell physiologyCellsCerebral Amyloid AngiopathyCerebrumClinicalContractile ProteinsCytoskeletal ModelingCytoskeletal ProteinsCytoskeletonDegenerative DisorderDepositionDevelopmentEndothelial CellsEndotheliumFigs - dietaryFutureGoalsGrowth FactorHemostatic functionImaging TechniquesImmuneIn VitroInterventionInvestigationKnowledgeLeadLigand BindingMaintenanceMediatingMicrocirculationMovementMyosin ATPasePathogenesisPericytesPermeabilityPhagocytesPharmacologic SubstancePlatelet-Derived Growth Factor beta ReceptorPlayProcessProteinsRecruitment ActivityRegulationResearchReverse Transcriptase Polymerase Chain ReactionRoleSignal TransductionSignaling MoleculeSmooth Muscle Actin Staining MethodStem cellsStructureSymptomsSystemTestingTight JunctionsToxic effectTransforming Growth Factor betaVascular Endothelial Growth FactorsWestern Blottingcapillaryimprovedmigrationmonomerneurovascular unitprotein expression
项目摘要
DESCRIPTION (provided by applicant): Pericytes are small cells located outside of brain microvessels between the endothelial cell layer and the parenchyma. As part of the neurovascular unit, pericytes have a substantial range of functions including contractile, immune, phagocytic and stem cell functions, in addition to contributing to blood-brain barrier (BBB) maintenance and hemostasis. One pathological hallmark of Alzheimer's disease (AD) is a compromised BBB characterized by significant reductions in pericytes on the exterior walls of endothelia. Pericyte coverage on endothelia is necessary for normal BBB functioning and the relationship between destruction of these cells and the development and progression of AD symptoms is currently not well understood. Understanding the significance of pericyte functioning in pathological conditions such as AD will lead to the development of future pharmaceutical interventions and improved treatment. The objective of this study is to understand the mechanisms and processes that lead to reduced coverage of pericytes on the endothelial wall and the resulting weakening of the BBB in degenerative conditions such as AD. Aim 1 is to determine if A¿ decreases PDGFR¿ and signaling molecules involved in pericyte-mediated BBB integrity regulation, leading to a compromised BBB in AD. If PDGFR¿ controls the recruitment of pericytes to vessel wall, then reduced expression of PDGFR¿ induced by A¿ will help explain the loss or impaired recruitment of pericytes outside the endothelial wall in AD.
If TGF¿, VEGF, and angiopoietin-1/-2 maintain BBB tight junction and paracellular permeability, then decreased secretion of these molecules from pericytes by A¿ will reveal an additional unknown mechanism leading to the compromise and leaks of the BBB in AD. We will examine the expression and translocation of these molecules using RT-PCR, Western blot and quantitative imaging techniques. Aim 2 is to determine if A¿ alters contractile and cytoskeletal proteins, therefore decreasing mobility, adhesion, and migration ability of pericytes, leading to impaired recruitment of pericytes to endothelia. Pericyte movement to endothelial cells is pivotal in vascular development and maintenance. Given that cytoskeletal and contratile proteins play key roles in cell shape, contraction, mobility and BBB permeability regulation, then our investigation of these proteins' expression, including alpha-smooth muscle actin (¿ -SMA) and myosin, and related actin cytoskeletal reorganization in the presence of A¿ will indicate that fewer pericytes are recruited to endothelia. Using in vitro capillary-like structures, we will idenify the rate-limiting step and key-signaling molecules in pericyte adhesion and migration affected by A¿. The rate-limiting step would be the ideal target for therapies.
PUBLIC HEALTH RELEVANCE: This proposed project will significantly increase our understanding of the role of pericytes and pericyte-A¿ interaction in regulating and maintaining the integrity of the brain's microvascular system in pathological conditions such as Alzheimer's disease (AD). It will also provide useful information for the development of future pharmaceutical interventions targeting pericyte protection in the treatment of AD.
描述(由申请人提供):周细胞是位于脑微血管外的小细胞,位于内皮细胞层和实质之间。周细胞作为神经血管单元的一部分,除了有助于血脑屏障(BBB)维持和止血外,还具有广泛的功能,包括收缩、免疫、吞噬和干细胞功能。阿尔茨海默病(AD)的一个病理标志是血脑屏障受损,其特征是内皮细胞外壁周细胞显著减少。内皮上的周细胞覆盖是血脑屏障正常功能所必需的,这些细胞的破坏与AD症状的发生和进展之间的关系目前尚不清楚。了解周细胞功能在AD等病理条件下的意义将导致未来药物干预和改进治疗的发展。本研究的目的是了解在退行性疾病(如阿尔茨海默病)中导致内皮壁上周细胞覆盖减少和血脑屏障减弱的机制和过程。目的1是确定A¿是否降低PDGFR¿和参与周细胞介导的血脑屏障完整性调节的信号分子,导致AD患者血脑屏障受损。如果PDGFR¿控制周细胞向血管壁的募集,那么A¿诱导的PDGFR¿表达降低将有助于解释AD内皮壁外周细胞募集的损失或受损。
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 }}
Donghui Zhu其他文献
Donghui Zhu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('Donghui Zhu', 18)}}的其他基金
Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease
镁在阿尔茨海默病神经炎症中的分子机制和功能作用
- 批准号:
10180843 - 财政年份:2019
- 资助金额:
$ 14.25万 - 项目类别:
Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease
镁在阿尔茨海默病神经炎症中的分子机制和功能作用
- 批准号:
10392710 - 财政年份:2019
- 资助金额:
$ 14.25万 - 项目类别:
Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease
镁在阿尔茨海默病神经炎症中的分子机制和功能作用
- 批准号:
10623230 - 财政年份:2019
- 资助金额:
$ 14.25万 - 项目类别:
Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease
镁在阿尔茨海默病神经炎症中的分子机制和功能作用
- 批准号:
10621554 - 财政年份:2019
- 资助金额:
$ 14.25万 - 项目类别:
Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease
镁在阿尔茨海默病神经炎症中的分子机制和功能作用
- 批准号:
10418762 - 财政年份:2019
- 资助金额:
$ 14.25万 - 项目类别:
Molecular Mechanism and Functional Role of Magnesium in Neuroinflammation in Alzheimer's Disease
镁在阿尔茨海默病神经炎症中的分子机制和功能作用
- 批准号:
10017824 - 财政年份:2019
- 资助金额:
$ 14.25万 - 项目类别:
Magnesium and alloying elements on vascular cells health
镁和合金元素对血管细胞健康的影响
- 批准号:
8854625 - 财政年份:2015
- 资助金额:
$ 14.25万 - 项目类别:
Magnesium and alloying elements on vascular cells health
镁和合金元素对血管细胞健康的影响
- 批准号:
9130833 - 财政年份:2015
- 资助金额:
$ 14.25万 - 项目类别:
Brain Pericyte and Amyloid-beta Peptide Interaction
脑周细胞和淀粉样蛋白-β 肽相互作用
- 批准号:
8539524 - 财政年份:2012
- 资助金额:
$ 14.25万 - 项目类别:
相似海外基金
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y004841/1 - 财政年份:2024
- 资助金额:
$ 14.25万 - 项目类别:
Research Grant
Defining a role for non-canonical mTORC1 activity at focal adhesions
定义非典型 mTORC1 活性在粘着斑中的作用
- 批准号:
BB/Y001427/1 - 财政年份:2024
- 资助金额:
$ 14.25万 - 项目类别:
Research Grant
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y005414/1 - 财政年份:2024
- 资助金额:
$ 14.25万 - 项目类别:
Research Grant
Development of a single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions.
开发一次性、即用型、无菌、双室、双注射器可喷雾水凝胶,以防止术后心脏粘连。
- 批准号:
10669829 - 财政年份:2023
- 资助金额:
$ 14.25万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10587090 - 财政年份:2023
- 资助金额:
$ 14.25万 - 项目类别:
Improving Maternal Outcomes of Cesarean Delivery with the Prevention of Postoperative Adhesions
通过预防术后粘连改善剖宫产的产妇结局
- 批准号:
10821599 - 财政年份:2023
- 资助金额:
$ 14.25万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10841832 - 财政年份:2023
- 资助金额:
$ 14.25万 - 项目类别:
Prevention of Intraabdominal Adhesions via Release of Novel Anti-Inflammatory from Surface Eroding Polymer Solid Barrier
通过从表面侵蚀聚合物固体屏障中释放新型抗炎剂来预防腹内粘连
- 批准号:
10532480 - 财政年份:2022
- 资助金额:
$ 14.25万 - 项目类别:
I-Corps: A Sprayable Tissue-Binding Hydrogel to Prevent Postsurgical Cardiac Adhesions
I-Corps:一种可喷雾的组织结合水凝胶,可防止术后心脏粘连
- 批准号:
10741261 - 财政年份:2022
- 资助金额:
$ 14.25万 - 项目类别:
Sprayable Polymer Blends for Prevention of Site Specific Surgical Adhesions
用于预防特定部位手术粘连的可喷涂聚合物共混物
- 批准号:
10674894 - 财政年份:2022
- 资助金额:
$ 14.25万 - 项目类别: