Department of Rheumatic and Immunologic Diseases/A50, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Semin Arthritis Rheum. 2013 Aug;43(1):125-30. doi: 10.1016/j.semarthrit.2012.12.005. Epub 2013 Jan 24.
To systematically review literature about the structure and function of nucleotide-binding oligomerization domain containing 2 (NOD2) and its disease association.
The English literature was searched using keywords "NOD2" and "disease". Relevant original and review articles were reviewed.
NOD2 is an intracellular protein and shares similar molecular structure with NOD1, pyrin, and cryopyrin. There are more than 100 NOD2 gene mutations, some of which have been linked to diseases such as Crohn disease, Blau syndrome, and NOD2-associated autoinflammatory disease (NAID). The NOD2 variants located in the leucine-rich repeat (LRR) region are susceptible to Crohn disease, and the variants in the nucleotide-binding domain (NBD) and in between the NBD and LRR are associated with Blau syndrome and NAID, respectively. No disease association with the gene variants has been found in rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis/psoriatic arthritis, adult sarcoidosis, granulomatous polyangiitis, or multiple sclerosis. The potential association of the NOD2 variants with graft-versus-host-disease remains controversial. NOD2 functions mainly through RICK or RIP2 to activate p38 mitogen-activated protein kinases and NF-κB, resulting in inflammatory response, and enhanced autophagic activity. Biologic therapy may be beneficial for NOD2-associated diseases, and new drug development may be realized based upon the signaling pathways.
NOD2 gene mutations are associated with several diseases, and some of the mutations are of diagnostic value in Blau disease and NAID. To understand the NOD2 function, disease association, and its pathogenesis is important given the ever increasing clinical significance of NOD2.
系统回顾核苷酸结合寡聚化结构域 2（NOD2）的结构和功能及其与疾病的关联的文献。
使用关键词“NOD2”和“疾病”检索英文文献。综述了相关的原始和综述文章。
NOD2 是一种细胞内蛋白，与 NOD1、pyrin 和 cryopyrin 具有相似的分子结构。有超过 100 种 NOD2 基因突变，其中一些与克罗恩病、Blau 综合征和 NOD2 相关自身炎症性疾病（NAID）等疾病有关。位于富含亮氨酸重复序列（LRR）区域的 NOD2 变异体易患克罗恩病，位于核苷酸结合域（NBD）和 NBD 与 LRR 之间的变异体分别与 Blau 综合征和 NAID 相关。尚未发现基因变异与类风湿关节炎、系统性红斑狼疮、强直性脊柱炎、银屑病/银屑病关节炎、成人结节病、肉芽肿性多血管炎或多发性硬化症有关。NOD2 变异体与移植物抗宿主病的潜在关联仍存在争议。NOD2 主要通过 RICK 或 RIP2 激活 p38 丝裂原活化蛋白激酶和 NF-κB，从而导致炎症反应和增强自噬活性。生物治疗可能对 NOD2 相关疾病有益，并且可能基于信号通路实现新药的开发。
NOD2 基因突变与多种疾病相关，其中一些突变对 Blau 病和 NAID 具有诊断价值。鉴于 NOD2 的临床意义不断增加，了解 NOD2 的功能、疾病关联及其发病机制非常重要。
