Molecular mechanism of NLRP3 inflammasome activation
NLRP3炎症小体激活的分子机制
基本信息
- 批准号:10612352
- 负责人:
- 金额:$ 38.01万
- 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
- 起止时间:2020-05-04 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:ATP phosphohydrolaseAlzheimer&aposs DiseaseAtherosclerosisBindingCASP1 geneCrohn&aposs diseaseDataDevelopmentDiabetes MellitusDiseaseEventGoalsGoutIL18 geneIn VitroInflammasomeInflammatoryInheritedInnate Immune SystemInterleukin-1 betaInvestigationLinkMacrophageMediatingMolecularNatural ImmunityPathogenesisPathway interactionsPeptidesPeriodicalsPhosphorylationPhosphotransferasesPotassiumProtein KinaseProteinsRegulationRoleSignal TransductionStimulusSurfaceSyndromeTestingTherapeutic Interventionautoinflammatoryhuman diseasein vivoinnovationinsightmolecular targeted therapiesnovelnovel therapeutic intervention
项目摘要
Project Summary
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) is a critical component of the
innate immune system that forms the NLRP3 inflammasome, an intracellular molecular platform
that drives caspase-1 activation and the secretion of biologically active IL-1β and IL-18. In addition
to its protective role in innate immunity, aberrant activation of the NLRP3 inflammasome
contributes to the pathogenesis of several inherited and acquired inflammatory disorders, such
as Cryopyrin-associated autoinflammatory syndrome, gout, Crohn's disease, Alzheimer's
disease, diabetes and atherosclerosis. Despite extensive investigation, the molecular mechanism
leading to NLRP3 inflammasome activation remains elusive. Recently, the protein kinase Nek7
has been found to mediate NLRP3 inflammasome activation independently of its kinase activity.
However, it is unknown how Nek7 is mechanistically linked to NLRP3 inflammasome activation.
Our recent studies implicate a critical role for Nek7 phosphorylation in NLRP3 inflammasome
activation. In this application we aim to elucidate the molecular mechanism of Nek7-mediated
NLRP3 inflammasome activation and determine the role of a novel regulator in this pathway. Our
results are expected to provide new mechanistic insights into NLRP3 inflammasome activation
and might guide the development of novel therapeutic strategies for treating NLRP3-driven
inflammatory diseases.
项目概要
含有 NAHT、LRR 和 PYD 结构域的蛋白 3 (NLRP3) 是
先天免疫系统形成 NLRP3 炎性体(一种细胞内分子平台)
驱动 caspase-1 激活以及具有生物活性的 IL-1β 和 IL-18 的分泌。此外
其在先天免疫中的保护作用,NLRP3 炎症小体的异常激活
导致多种遗传性和获得性炎症性疾病的发病机制,例如
如冷吡啶相关自身炎症综合征、痛风、克罗恩病、阿尔茨海默病
疾病、糖尿病和动脉粥样硬化。尽管进行了广泛的研究,分子机制
导致 NLRP3 炎症小体激活的机制仍然难以捉摸。最近,蛋白激酶Nek7
已发现独立于其激酶活性来介导 NLRP3 炎性体激活。
然而,Nek7 与 NLRP3 炎症小体激活的机制尚不清楚。
我们最近的研究表明 Nek7 磷酸化在 NLRP3 炎症体中的关键作用
激活。在本申请中,我们旨在阐明 Nek7 介导的分子机制
NLRP3 炎症小体激活并确定新型调节剂在该途径中的作用。我们的
研究结果有望为 NLRP3 炎症小体激活提供新的机制见解
并可能指导开发治疗 NLRP3 驱动的新治疗策略
炎症性疾病。
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)
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Yuan He其他文献
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{{ truncateString('Yuan He', 18)}}的其他基金
Structure and Mechanism of Eukaryotic Transcription Regulation
真核生物转录调控的结构和机制
- 批准号:
10445554 - 财政年份:2022
- 资助金额:
$ 38.01万 - 项目类别:
Structure and Mechanism of Eukaryotic Transcription Regulation
真核生物转录调控的结构和机制
- 批准号:
10625407 - 财政年份:2022
- 资助金额:
$ 38.01万 - 项目类别:
Structure and Mechanism of Non-Homologous End Joining
非同源末端连接的结构和机制
- 批准号:
10546447 - 财政年份:2020
- 资助金额:
$ 38.01万 - 项目类别:
Molecular mechanism of NLRP3 inflammasome activation
NLRP3炎症小体激活的分子机制
- 批准号:
10158435 - 财政年份:2020
- 资助金额:
$ 38.01万 - 项目类别:
Structure and Mechanism of Non-Homologous End Joining
非同源末端连接的结构和机制
- 批准号:
10331036 - 财政年份:2020
- 资助金额:
$ 38.01万 - 项目类别:
Molecular mechanism of NLRP3 inflammasome activation
NLRP3炎症小体激活的分子机制
- 批准号:
10390480 - 财政年份:2020
- 资助金额:
$ 38.01万 - 项目类别:
ROLE OF NEK7 PROTEIN IN NLRP3 INFLAMMASOME ACTIVATION AND INFLAMMATION
NEK7 蛋白在 NLRP3 炎症小体激活和炎症中的作用
- 批准号:
9179168 - 财政年份:2017
- 资助金额:
$ 38.01万 - 项目类别: