Neutrophil extracellular traps and neuropsychiatric lupus: Signaling pathways involved in NET formation and mechanisms affecting the central nervous system

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe complication of systemic lupus erythematosus (SLE) that affects the central or peripheral nervous system. The clinical management of NPSLE faces significant challenges due to the absence of specific diagnostic biomarkers and the lack of standardized, evidence-based diagnostic and therapeutic protocols. Therefore, a comprehensive understanding of the pathogenesis of NPSLE and the exploration of novel therapeutic targets have become urgent priorities in current research. Recent studies have demonstrated that neutrophils and their hallmark product, neutrophil extracellular traps (NETs), play a central role in various pathological processes of NPSLE, with blood-brain barrier (BBB) disruption and the subsequent inflammatory cascade being particularly critical. This paper provides a systematic review of the molecular regulatory network of neutrophils in NPSLE, focusing on the mechanisms by which neutrophils mediate neuroimmune microenvironmental disorders through BBB damage, with the goal of offering a theoretical foundation for the precise diagnosis and treatment of this disease.