Moreno L, Gatheral T
Ciber de Enfermedades Respiratorias (CIBERES), Bunyola, Spain; Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
Br J Pharmacol. 2013 Oct;170(3):475-85. doi: 10.1111/bph.12300.
The nucleotide-binding oligomerization domain 1 (NOD1) protein is an intracellular receptor for breakdown products of peptidoglycan (PGN), an essential bacterial cell wall component. NOD1 responds to γ-D-glutamyl-meso-diaminopimelic acid, which is an epitope unique to PGN structures from all Gram-negative bacteria and certain Gram-positive bacteria. Upon ligand recognition, NOD1 undergoes conformational changes and self-oligomerization mediated by the nucleotide-binding NACHT domains, followed by the recruitment and activation of the serine threonine kinase receptor-interacting protein 2 leading to the activation of NF-κB and MAPK pathways and induction of inflammatory genes. Much of our knowledge is derived from seminal studies using mice deficient in NOD1 and confirming an essential role for NOD1 in the host immune response against gastrointestinal and respiratory pathogens. In addition, recent studies have revealed a role for intracellular NOD1 receptors in the regulation of vascular inflammation and metabolism. This review will discuss our current understanding of intracellular NOD1 receptors in host immunity and chronic inflammatory disorders with a focus on cardiovascular diseases. Although therapeutic advances may have to wait until the complex interplay with pathogens, danger signals, other pattern recognition receptors and overlapping metabolic pathways is further unravelled, the steadily growing body of knowledge suggest that NOD1 antagonism might represent attractive candidate to reduce excessive inflammation associated to intestinal, cardiovascular and metabolic diseases.
核苷酸结合寡聚化结构域1（NOD1）蛋白是肽聚糖（PGN）分解产物的细胞内受体，PGN是细菌细胞壁的一种重要成分。NOD1对γ-D-谷氨酰-内消旋二氨基庚二酸有反应，这是所有革兰氏阴性菌和某些革兰氏阳性菌PGN结构特有的一个表位。在配体识别后，NOD1会发生构象变化并由核苷酸结合NACHT结构域介导自寡聚化，随后募集并激活丝氨酸苏氨酸激酶受体相互作用蛋白2，导致NF-κB和MAPK信号通路激活以及炎症基因的诱导。我们的许多知识来自于对NOD1缺陷小鼠的开创性研究，这些研究证实了NOD1在宿主针对胃肠道和呼吸道病原体的免疫反应中的重要作用。此外，最近的研究揭示了细胞内NOD1受体在血管炎症和代谢调节中的作用。本综述将讨论我们目前对宿主免疫和慢性炎症性疾病中细胞内NOD1受体的理解，重点是心血管疾病。尽管治疗进展可能要等到与病原体、危险信号、其他模式识别受体和重叠代谢途径之间复杂的相互作用进一步阐明之后，但不断增长的知识表明，NOD1拮抗作用可能是减少与肠道、心血管和代谢疾病相关的过度炎症的有吸引力的候选方法。
