Roles of NOD1 (NLRC1) and NOD2 (NLRC2) in innate immunity and inflammatory diseases.
Roles of NOD1 (NLRC1) and NOD2 (NLRC2) in innate immunity and inflammatory diseases.
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NOD1（NLRC1）和NOD2（NLRC2）在先天免疫和炎症性疾病中的作用。
DOI：
10.1042/bsr20120055
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发表时间：
2012-12
影响因子：
4
通讯作者：
Reed JC
中科院分区：
文献类型：
--
作者：
Correa RG;Milutinovic S;Reed JC
Nod1(核苷酸结合的寡聚化结构域1；NLRC[Nod-LRR(亮氨酸重复)家族与CARD(半胱氨酸酶招募结构域)1]}和NOD2(NLRC2)是NLR(NOD-LRR)家族中最重要的成员-蛋白质包含核苷酸结合的Nacht结构域和受体样LRR结构域。在人类中发现了20多个成员，NLRs是哺乳动物先天免疫系统的重要组成部分，是病原体和组织损伤所致的内源性分子的细胞内受体。Nod1和NOD2蛋白通过识别细菌的特定PG(肽聚糖)成分，作为微生物传感器工作。激活后，这些NLR家族成员启动信号转导机制，包括刺激核因子-κB(核因子-κB)、应激激酶、干扰素调节因子(IFF)和自噬。编码NOD1和NOD2基因的遗传性多态与越来越多的慢性炎症性疾病有关。事实上，使用一系列动物模型进行的研究已经揭示了NOD1和NOD2基因在炎症性疾病中的潜在作用。在本综述中，我们描述了NOD1和NOD2与各种自身免疫性和慢性炎症性疾病相关的最新实验结果，并讨论了针对这些NLR家族蛋白的新疗法的发展前景。
NOD1 {nucleotide-binding oligomerization domain 1; NLRC [NOD-LRR (leucine-rich repeat) family with CARD (caspase recruitment domain) 1]} and NOD2 (NLRC2) are among the most prominent members of the NLR (NOD-LRR) family –proteins that contain nucleotide-binding NACHT domains and receptor-like LRR domains. With over 20 members identified in humans, NLRs represent important components of the mammalian innate immune system, serving as intracellular receptors for pathogens and for endogenous molecules elaborated by tissue injury. NOD1 and NOD2 proteins operate as microbial sensors through the recognition of specific PG (peptidoglycan) constituents of bacteria. Upon activation, these NLR family members initiate signal transduction mechanisms that include stimulation of NF-κB (nuclear factor-κB), stress kinases, IRFs (interferon regulatory factors) and autophagy. Hereditary polymorphisms in the genes encoding NOD1 and NOD2 have been associated with an increasing number of chronic inflammatory diseases. In fact, potential roles for NOD1 and NOD2 in inflammatory disorders have been revealed by investigations using a series of animal models. In the present review, we describe recent experimental findings associating NOD1 and NOD2 with various autoimmune and chronic inflammatory disorders, and we discuss prospects for development of novel therapeutics targeting these NLR family proteins.