Mechanisms of NLRP3 inflammasome activation

NLRP3炎症小体激活机制

• 批准号: 10796165
• 负责人: Michael R. Nichols
• 金额: $ 45.93万
• 依托单位: UNIVERSITY OF MISSOURI-ST. LOUIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10796165
• 关键词: Academic Research Enhancement Awards; Alzheimer' s Disease; Amyloid beta-Protein; Binding; Biochemical; Biophysics; CASP1 gene; Catalysis; Cells; Complex; Confocal Microscopy; Data; Disease; Elements; Enzymes; Future; Heart Diseases; Human; In Vitro; Inflammasome; Inflammatory; Innate Immune System; Institution; Interleukin-1 beta; Investigation; Knowledge; Lead; Link; Medical; Microglia; Molecular; Molecular Conformation; Neurodegenerative Disorders; Pattern; Process; Production; Proteins; Recombinants; Regulation; Research; Role; Students; System; Testing; Therapeutic; Training and Education; Transfection; Viral; Work; cytokine; experience; improved; interest; pathogen; research study; response; undergraduate student

PROJECT SUMMARY/ABSTRACT An important component of the mammalian innate immune system is the NLRP3 inflammasome, an intracellular complex of three proteins that, upon activation, produces the cytokine interleukin-1β. Activation of the NLRP3 complex can occur via internalization of a growing number of endogenous human molecules, referred to as damage-associated molecular patterns (DAMPs). The absolute mechanisms of how DAMPs trigger NLRP3 inflammasome activation is not fully understood. There is convincing evidence that direct interactions between internalized DAMPs and inflammasome proteins may be one of these mechanisms. This high-impact R15 AREA application will seek to characterize direct interactions between the well-known DAMP amyloid-β (Aβ) and inflammasome proteins (1) in vitro and (2) in cellular systems. The last objective will be to link these direct interactions with inflammasome activation. These findings will have implications for the treatment of inflammatory, neurodegenerative, and heart diseases.

项目摘要/摘要 哺乳动物先天免疫系统的重要组成部分是NLRP3炎症体，一个细胞内 激活后三种蛋白质的复合物，会产生细胞因子白细胞介素1β。激活NLRP3 复合物可以通过越来越多的内源性人分子的内在化发生，称为 损伤相关的分子模式（湿）。湿度触发NLRP3的绝对机制 炎症体激活尚不完全了解。有令人信服的证据表明 内部潮湿和炎性蛋白可能是这些机制之一。这个高影响R15区域 应用将寻求表征众所周知的湿润淀粉样蛋白β（Aβ）和 炎性蛋白（1）体外和（2）在细胞系统中。最后一个目标是将这些直接联系起来 与炎症体激活的相互作用。这些发现将对治疗 炎症，神经退行性和心脏病。