Kaneko Naoe, Iwasaki Tomoyuki, Ito Yuki, Takeda Hiroyuki, Sawasaki Tatsuya, Morikawa Shinnosuke, Nakano Naoko, Kurata Mie, Masumoto Junya
Department of Pathology, Ehime University Graduate School of Medicine and Proteo-Science Center, Shitsukawa 454, Toon, 791-0295 Ehime Japan.
Divison of Proteo-Drug-Discovery Sciences, Ehime University Proteo-Science Center, Bunkyocho 3, Matsuyama, 790-8577 Ehime Japan.
Inflamm Regen. 2017 May 3;37:9. doi: 10.1186/s41232-017-0040-y. eCollection 2017.
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.
炎症小体通常由一个核苷酸结合寡聚化结构域样受体、凋亡相关斑点样蛋白和前半胱天冬酶-1组成，最近被鉴定为一种巨大的细胞内复合物，它在白细胞介素-1成熟或特定生理功能中起关键作用。两种核苷酸结合寡聚化结构域样受体，如含核苷酸结合寡聚化结构域蛋白（Nod）1和Nod2，与受体相互作用蛋白丝氨酸-苏氨酸激酶（RIPK）2相互作用，并伴有Iκ-B激酶（IKK）复合物，以构建结节小体，从而导致核因子（NF）-κB激活。炎症小体或结节小体的异常激活会引发自身炎症性疾病。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点。我们的目标是在无细胞系统中开发重组炎症小体，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组炎症小体。
