Neutrophil extracellular trap-associated proteins (NET-associated proteins)

Neutrophil extracellular traps (NETs) are extracellular fibers composed of a DNA scaffold decorated with histones and granular proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), and cathepsin G (Brinkmann et al., 2004, Science). These structures are released by neutrophils during a specialized cell death process called NETosis to trap and neutralize pathogens; however, their excessive or persistent presence is a major driver of tissue damage in chronic inflammatory and autoimmune diseases (Papayannopoulos, 2018, Nature Reviews Immunology). NET-associated proteins like NE and MPO promote inflammatory cascades and contribute to the formation of immunothrombosis, while citrullinated histones (produced via PAD4 activity) act as potent autoantigens in conditions like rheumatoid arthritis and systemic lupus erythematosus (Knight et al., 2013, Science Translational Medicine). Therapeutic targeting of these proteins involves degrading the DNA backbone with DNases, inhibiting the enzymatic activity of associated proteases, or blocking the PAD4-mediated chromatin decondensation required for NET formation (Jorch & Kubes, 2017, Nature Medicine). By modulating these components, drug candidates aim to mitigate the pathological effects of NETs in diseases ranging from sepsis and COVID-19 to metastatic cancer and cardiovascular disorders.

Other names

NET proteinsNeutrophil extracellular trap componentsNET-bound proteinsNETosis-related proteins

Degradation of the DNA scaffold (DNase), inhibition of neutrophil proteases (NE inhibitors), and inhibition of peptidylarginine deiminase 4 (PAD4 inhibitors) to prevent chromatin decondensation and NET release.