Netrin-1: An emerging player in inflammatory diseases

• Published in: Cytokine & growth factor reviews 2022-04, Vol.64, p.46-56
• Main Authors: Xia, Xueli, Hu, Zhigang, Wang, Shengjun, Yin, Kai
• Format: Article
• Language: English
• Subjects: Axon guidance molecule; Inflammatory diseases; Netrin-1; Receptor
• ISSN: 1359-6101
• DOI: 10.1016/j.cytogfr.2022.01.003

Netrin-1 is a member of the laminin-like protein family and was initially identified as a potent chemotactic molecule involved in axonal guidance and cell migration during embryonic development. Many studies have focused on the non-neural effects of netrin-1, and the results revealed that netrin-1 may be extensively involved in the regulation of angiogenesis, inflammation, tissue remodeling, and cancer. The pathogenic or protective effect of netrin-1 suggests that it may be a potential therapeutic target in multiple diseases. Netrin-1 plays different roles by interacting with its receptors, such as deleted in colorectal cancer (DCC)/neogenin and the uncoordinated-5 homolog family members (UNC5). Interestingly, contradictory actions in certain physiological pathways serve to highlight its manifold and often opposite effects on numerous physiological and pathophysiological processes. Netrin-1 regulates inflammation and leukocyte infiltration, suggesting roles for netrin-1 in the immune response. In this study, we review recent advances in the understanding of netrin-1 and its receptors in many inflammatory diseases and look forward to the bioavailability of netrin-1 for the future. [Display omitted] •Netrin-1 contains a highly conserved N-terminal LN domain, domain V and a small positively charged C-terminal domain.•The netrin-1-receptor axis is usually dynamically fine-tuned at specific locations and times.•Netrin-1 engages several different receptors to activate chemotropic responses and adhesive mechanisms in non-neural systems.•Netrin-1 involved in angiogenesis, leukocyte migration, and macrophage phenotype switching.