Neuroglial Adhesin 1 (NEGR1): A Novel Perspective on Exploring Pathogenesis and Therapeutic Targets in Pre-eclampsia

Preeclampsia (PE) is a severe hypertensive disorder of pregnancy and one of the leading causes of maternal and perinatal mortality worldwide, with a complex pathogenesis. Neuronal Adhesion Molecule 1 (NEGR1), a glycosylated phosphoinositide-anchored protein involved in cell adhesion and neuronal growth, most current research has focused on the field of malignant tumours, and its function in the reproductive and perinatal fields remains unclear.Recent research indicates that NEGR1 gene deletion significantly activates the phosphatidylinositol 3-kinase/ Protein Kinase B (PI3K/AKT) signalling pathway, thereby promoting the M2 phenotype polarisation of macrophages at the placental or maternal-foetal interface and stimulating substantial IL-10 release. This discovery offers a novel perspective for understanding the immunological pathogenesis of PE. This review aims to systematically elucidate the novel mechanism by which NEGR1 influences macrophage polarisation and IL-10 release through regulating the PI3K/AKT pathway, and to explore in depth the role of this mechanism in the pathogenesis of pre-eclampsia.