Role of p62-Mediated Endothelial FA-Phagy in Intracranial Aneurysms
p62 介导的内皮 FA 吞噬在颅内动脉瘤中的作用
基本信息
- 批准号:10574825
- 负责人:
- 金额:$ 23.4万
- 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:2023-01-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AffinityAneurysmAreaAutophagocytosisAutophagosomeBindingBiological AssayBlood VesselsBrain AneurysmsCRISPR/Cas technologyCause of DeathCerebrovascular systemCessation of lifeCircle of WillisClinical TrialsDataDegradation PathwayDevelopmentDigestionDiseaseDrug TargetingEndothelial CellsEndotheliumEventExtracellular MatrixExtravasationFocal AdhesionsFoundationsGenesGoalsHealthHumanImpairmentIncidenceIntracranial AneurysmKineticsKnowledgeMediatingMethodsMissionMonitorMusNamesPathogenesisPathogenicityPathologicPathway interactionsPermeabilityPhosphorylationPhosphotransferasesPlayProcessPropertyPublic HealthReceptor GeneReportingResearchRoleRuptureStainsSubarachnoid HemorrhageSystemTANK-binding kinase 1TestingTracerUnited States National Institutes of HealthVariantVascular DiseasesVascular Endothelial CellVascular PermeabilitiesWorkZebrafishbrain endothelial cellburden of illnesscerebrovasculardisabilityexperimental studygain of functionimprovedin vivoinhibitorinnovationknock-downloss of functionmimeticsmouse modelnew therapeutic targetnovelnovel therapeuticspreservationpreventreceptorreceptor functionrecruitstroke patient
项目摘要
PROJECT SUMMARY
An intracranial aneurysm (IA) is a balloon-like bulge in a weakened area of a blood vessel in the brain.
Rupture of an IA leads to a subarachnoid hemorrhage, a major cause of death and disability in stroke
patients. However, the underlying pathogenic mechanisms that contribute to IA development are poorly
understood, which greatly impedes attempts to identify novel therapeutic targets for the disease.
Cerebrovascular integrity plays a pivotal role in IA development. In particular, focal adhesion (FA), a
property that enables endothelial cells to adhere to their extracellular matrix, is required for
cerebrovascular integrity. Recently, we named FA-phagy for “selective autophagy of FA” which can
regulate FA stability. Moreover, we identified p62 as the major cargo receptor for FA-phagy in endothelial
cells. Our central hypothesis is that p62-mediated endothelial FA-phagy impairs cerebrovascular integrity
and thus contributes to IA development. This hypothesis will be tested in two specific aims: 1) determine
the role of p62-mediated endothelial FA-phagy in cerebrovascular integrity and intracranial aneurysm
development; and 2) define the cargo recognition mechanisms in p62-mediated endothelial FA-phagy.
These proposed experiments may provide a firm scientific foundation for further treating IA disease by
targeting p62-mediated cargo recognition mechanisms. Importantly, this targeting cargo recognition
mechanism may precisely interfere with a specific type of autophagy and thus shift the current paradigm
on autophagy manipulation in vascular diseases, since most inhibitors in clinical trials block autophagic
core machinery that is shared in all types of autophagy, thus leading to unwanted consequences. Our
project's aims may collectively establish anti-FA-phagy strategy as a novel therapy for IA and potentially
for many other diseases due to the loss of vascular integrity.
项目总结
颅内动脉瘤(IA)是大脑中血管薄弱区域内的气球状隆起。
颈内动脉破裂导致蛛网膜下腔出血,这是导致中风死亡和残疾的主要原因
病人。然而,导致IA发生的潜在致病机制很差。
这极大地阻碍了为该病确定新的治疗靶点的努力。
脑血管完整性在IA的发展中起着至关重要的作用。特别是,焦点粘连(FA),a
使内皮细胞能够与其细胞外基质黏附的特性是
脑血管完整性。最近,我们将FA-phagy命名为“FA选择性自噬”,它可以
调节FA的稳定性。此外,我们发现p62是内皮细胞中FA-吞噬作用的主要受体。
细胞。我们的中心假设是p62介导的内皮FA吞噬功能损害脑血管完整性
从而为信息技术的发展做出了贡献。这一假设将在两个具体目标中得到检验:1)确定
P62介导的内皮细胞FA吞噬在脑血管完整性和颅内动脉瘤中的作用
发展;以及2)确定p62介导的内皮FA吞噬中的货物识别机制。
这些拟议的实验可能为进一步治疗IA病提供坚实的科学基础
靶向p62介导的货物识别机制。重要的是,这一目标货物识别
机制可能精确地干扰特定类型的自噬,从而改变当前的范式
关于血管疾病中的自噬操作,因为临床试验中的大多数抑制剂都阻断了自噬
在所有类型的自噬中共享的核心机制,从而导致不想要的后果。我们的
该项目的目标可能共同建立反FA吞噬策略,作为IA的一种新疗法,并有可能
由于血管完整性的丧失而导致的许多其他疾病。
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 }}
Yanning Rui其他文献
Yanning Rui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('Yanning Rui', 18)}}的其他基金
Role of Selective Autophagy of Focal Adhesion in Intracranial Aneurysm
局部粘连选择性自噬在颅内动脉瘤中的作用
- 批准号:
10586692 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
相似海外基金
Establishment of human abdominal aortic aneurysm wall strength prediction model using Ex Vivo Superparamagnetic Iron Oxide–Enhanced Magnetic Resonance Imaging
利用Ex Vivo超顺磁性氧化铁建立人体腹主动脉瘤壁强度预测模型
- 批准号:
23K08226 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Endothelial Cell Reprogramming in Familial Intracranial Aneurysm
家族性颅内动脉瘤的内皮细胞重编程
- 批准号:
10595404 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Vascular Smooth Muscle Protein Quality Control and Aortic Aneurysm Formation
血管平滑肌蛋白质量控制与主动脉瘤形成
- 批准号:
10714562 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Enhanced Biochemical Monitoring for Aortic Aneurysm Disease
加强主动脉瘤疾病的生化监测
- 批准号:
10716621 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Role of mechanical heterogeneity in cerebral aneurysm growth and rupture
机械异质性在脑动脉瘤生长和破裂中的作用
- 批准号:
10585539 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Study on development of prophylaxis for recanalization after coil embolization of cerebral aneurysm and elucidation of its mechanisms
脑动脉瘤弹簧圈栓塞术后再通预防措施的研究进展及机制阐明
- 批准号:
23K08512 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Roles of aging and cellular senescence in the development of intracranial aneurysm rupture
衰老和细胞衰老在颅内动脉瘤破裂发展中的作用
- 批准号:
10680060 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Role of Selective Autophagy of Focal Adhesion in Intracranial Aneurysm
局部粘连选择性自噬在颅内动脉瘤中的作用
- 批准号:
10586692 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Vascular smooth muscle cell ferroptosis and abdominal aortic aneurysm
血管平滑肌细胞铁死亡与腹主动脉瘤
- 批准号:
10733477 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别:
Extracellular Vesicle Delivery System for Treatment of Abdominal Aortic Aneurysm
细胞外囊泡递送系统治疗腹主动脉瘤
- 批准号:
10751123 - 财政年份:2023
- 资助金额:
$ 23.4万 - 项目类别: