Mechanisms of NLRP3 inflammasome activation

项目总结/摘要 哺乳动物先天性免疫系统的重要组分是NLRP 3炎性体，其是一种细胞内炎性小体。 三种蛋白质的复合物，激活后产生细胞因子白细胞介素-1 β。NLRP 3的激活 复合物可以通过越来越多的内源性人类分子的内化而发生，称为内源性人类分子。 损伤相关分子模式（DAMPs）。DAMP如何触发NLRP 3的绝对机制 炎性小体激活尚未完全了解。有令人信服的证据表明， DAMPs和炎性小体蛋白的内化可能是这些机制之一。这个高影响力的R15区域 本申请将寻求表征众所周知的DAMP淀粉样蛋白-β（Aβ）和 炎性体蛋白（1）体外和（2）细胞系统。最后一个目标是将这些直接联系起来， 与炎性小体激活的相互作用。这些发现将对治疗 炎症、神经变性和心脏病。

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.