Mechanistic insights into neutrophil extracellular traps with emphasis on neurological diseases

Neutrophil extracellular traps (NETs) are web-like structures released by neutrophils, consisting of a DNA backbone embedded with histones and granular enzymes. Initially identified as an antimicrobial defense mechanism, NETs have increasingly attracted attention in recent years for their roles in various non-infectious diseases, particularly central nervous system (CNS) disorders. This review systematically elaborates on the mechanisms underlying NET formation and their bidirectional interactions with neuroinflammation. It highlights the critical involvement of NETs in the progression of diseases such as glioma, brain metastases, stroke, traumatic brain injury, and Alzheimer's disease through core pathways including disruption of the blood–brain barrier, promotion of thromboinflammation, mediation of immunosuppression, and direct neuronal damage. We further summarize potential therapeutic strategies targeting NETs and discuss their prospects as disease biomarkers. By organizing the field around shared neurovascular modules and disease-specific branches, and by distinguishing preclinical promise from human evidence, this review provides a translational framework for prioritizing NET-related biomarkers and therapeutic strategies in neurological diseases.