细胞表面受体神经纤毛蛋白-1（NRP1）的多方面信号传导：病理生理作用与治疗潜力

文献信息

中文摘要

神经纤毛蛋白-1（NRP1）是一种发育上保守的细胞表面受体，其功能是结合多种配体，如3类信号素和VEGF家族的若干成员，从而参与控制细胞迁移和运动的不同信号通路。由于其广泛表达，NRP1参与免疫功能、轴突导向、病毒进入、肿瘤进展和血管生成。NRP1在多种癌症类型中失调，并以背景依赖的方式在肿瘤细胞和肿瘤微环境（包括内皮、基质和免疫细胞区室）中促进肿瘤进展。NRP1还参与不同的自身免疫性疾病、嗅觉丧失和心血管疾病。噬菌体展示研究表明，含有C端CendR基序的肽可结合NRP1以实现组织穿透。除细胞穿透肽外，针对NRP1的单克隆抗体也是癌症治疗的一个有前景的靶点。重要的是，在SARS-CoV-2感染中，NRP1作为辅助宿主因子，病毒刺突蛋白的弗林蛋白酶切割暴露出一个可与NRP1结合的C端CendR基序，从而促进病毒进入。然而，NRP1并非与ACE2相当的独立受体，因此，靶向NRP1的抗病毒策略需要进一步研究。鉴于上述内容，本综述全面叙述了NRP1在不同疾病中的不同信号机制，以及如何利用这种细胞表面受体以各种治疗方法来对抗这些疾病。

英文摘要

Neuropilin-1 (NRP1) is a developmentally conserved cell surface receptor that functionally acts to bind various ligands like class 3 semaphorins and several members of the VEGF family to engage in different signaling pathways that control cell migration and motility. Due to its widespread expression, NRP1 is implicated in immune function, axonal guidance, viral entry, tumor progression and angiogenesis. NRP1 is dysregulated across multiple cancer types and promotes tumor progression in a context-dependent manner in tumor cells and the tumor microenvironment, including endothelial, stromal, and immune-cell compartments. NRP1 is also involved in different autoimmune disorders, anosmia, and cardiovascular disorders. Phage display studies revealed that peptides containing C-terminal CendR motifs engage NRP1 for tissue penetration. Apart from cell-penetrating peptides, monoclonal antibodies against NRP1 also present a promising target for cancer therapeutics. Importantly, NRP1 in SARS-CoV-2 infection act as an auxiliary host factor, and furin cleavage of the viral spike protein exposes a C-terminal CendR motif that can bind NRP1, thereby facilitating viral entry. However, NRP1 is not an independent receptor comparable to ACE2, thus, NRP1-targeted antiviral strategies need further investigations. Given the above, the review provides comprehensive narrative of different signaling mechanisms of NRP1 in different diseases and how this cell surface receptor can be utilized in various therapeutic approaches to combat these diseases.