Defensin alpha 1 (DEFA1)

Defensin alpha 1 (DEFA1), also known as human neutrophil peptide 1 (HNP-1), is a small cationic antimicrobial peptide mainly stored in the azurophilic granules of neutrophils[1][3][4][5]. It is a member of the defensin family, characterized by a conserved pattern of six cysteines forming three disulfide bonds that generate a stable, beta-sheet structure essential for microbicidal activity[2]. DEFA1 is produced as a precursor in promyelocytes, processed to the mature active form, and acts by directly disrupting microbial membranes (bacteria, fungi, viruses), inhibiting bacterial cell wall synthesis (via interactions with lipid II), and modulating immune processes such as cytokine and interferon induction (notably interleukin 6 and type I interferon)[1][2][3][5][6]. Its expression is subject to copy number variation, which has been associated with altered susceptibility to infectious and inflammatory diseases such as sepsis and cardiovascular disease[1][3]. Although primarily a direct innate defense effector, DEFA1 has shown potential as a biomarker and experimental therapeutic target for infection, inflammation, and certain cancers[1][3][5]. There are currently no approved drugs that target DEFA1, but synthetic analogs and modified peptides are under investigation for their antimicrobial and anti-inflammatory effects[2].

Other names

Neutrophil defensin 1Human neutrophil peptide 1 (HNP-1)Defensin alpha 2 (DEFA2)HP-1HP1HP-2HP2MRSDEF1HNP-2Myeloid-related sequence

Direct antimicrobial killing via membrane pore formation and disruption; Inhibition of bacterial cell wall synthesis (via binding lipid II); Immunomodulation (cytokine induction, dendritic cell activation); Inhibition of viral entry or uncoating.