Applications of reconstituted inflammasomes in a cell-free system to drug discovery and elucidation of the pathogenesis of autoinflammatory diseases.
Applications of reconstituted inflammasomes in a cell-free system to drug discovery and elucidation of the pathogenesis of autoinflammatory diseases.
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DOI：
10.1186/s41232-017-0040-y
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发表时间：
2017
影响因子：
8.1
通讯作者：
Masumoto J
中科院分区：
文献类型：
--
作者：
Kaneko N;Iwasaki T;Ito Y;Takeda H;Sawasaki T;Morikawa S;Nakano N;Kurata M;Masumoto J
炎症小体通常由 Nod 样受体、凋亡相关斑点样蛋白和 pro-caspase-1 组成，最近被鉴定为一种巨大的细胞内复合物，在 IL-1 成熟或特定生理功能中发挥着至关重要的作用。两种 Nod 样受体，例如含有核苷酸结合寡聚化结构域的蛋白 (Nod)1 和 Nod2，与受体相互作用蛋白丝氨酸-苏氨酸激酶 (RIPK)2 以及 Iκ-B 激酶 (IKK) 复合物相互作用，构建结节体，导致核因子 (NF)-κB 激活。炎症小体或结节体的异常激活会导致自身炎症性疾病。因此，炎症小体可能是治疗自身炎症性疾病的有吸引力的靶标。我们的目标是在无细胞系统中开发重建炎症小体，以发现特定的分子靶向药物并阐明自身炎症性疾病的分子发病机制。在这篇综述中，我们描述了无细胞系统中的重建炎症小体。
The inflammasome, typically consisting of a Nod-like receptor, apoptosis-associated speck-like protein, and pro-caspase-1, has recently been identified as a huge intracellular complex, which plays a crucial role in interleukin-1 maturation or specific physiological functions. Two Nod-like receptors, such as nucleotide-binding oligomerization domains-containing protein (Nod)1 and Nod2, interact with the receptor-interacting protein serine-threonine kinase (RIPK)2 accompanied by Iκ-B kinase (IKK) complexes to construct the nodosome, leading to nuclear factor (NF)-κB activation. The aberrant activation of inflammasomes or nodosomes causes autoinflammatory diseases. Therefore, inflammasomes may be attractive targets to treat autoinflammatory diseases. Our aim is to develop reconstituted inflammasomes in a cell-free system to discover specific molecular-target drugs and elucidate the molecular pathogenesis of autoinflammatory diseases. In this review, we describe reconstituted inflammasomes in a cell-free system.