expression. An artificial human theta-defensin, retrocyclin, was created by 'fixing' the pseudogene, and it was shown to be effective against HIV and other viruses, including herpes simplex virus and influenza A. They act primarily by preventing these viruses from entering their target cells. Also interesting is the effect of alpha-defensins on the exotoxin produced by anthrax (Bacillus anthracis). Chun Kim et al. showed how anthrax, which produces a metalloprotease lethal factor (LF) protein to target MAPKK, is vulnerable to human neutrophil protein-1 (HNP-1). This group showed HNP-1 to behave as a reversible noncompetitive inhibitor of LF. They have generally been considered to contribute to mucosal health; however, it is possible that these peptides can be considered biological factors that can be upregulated by bioactive compounds present in human breast milk. In this sense, the intestinal production of antimicrobial peptides as hBD2 and hBD4 by trefoil from milk might play an important role on neonate colonization, thereby enhancing the immune response of newborns against pathogens with which they may come in contact. Pathology The alpha defensin peptides are increased in chronic inflammatory conditions. Alpha defensin are increased in several cancers, including colorectal cancer. An imbalance of defensins in the skin may contribute to acne. A reduction of ileal defensins may predispose to Crohn's disease. In one small study, a significant increase in alpha defensin levels was detected in T cell lysates of schizophrenia patients; in discordant twin pairs, unaffected twins also had an increase, although not as high as that of their ill siblings. The authors suggested that alpha-defensin levels might prove a useful marker for schizophrenia risk. Defensins are found in the human skin during inflammatory conditions like psoriasis and also during wound healing. Applications Defensins At present, the widespread spread of antibiotic resistance requires the search and development of new antimicrobial drugs. From this point of view, defensins (as well as antimicrobial peptides in general) are of great interest. It was shown that defensins have pronounced antibacterial activity against a wide range of pathogens. In addition, defensins can enhance the effectiveness of conventional antibiotics. Defensin-mimetics Defensin mimetics, also called host defense peptide (HDP) mimetics, are completely synthetic, non-peptide, small molecule structures that mimic defensins in structure and activity. Similar molecules, such as brilacidin, are being developed as antibiotics, anti-inflammatories for oral mucositis, and antifungals, especially for candidiasis. See also Host defense peptides, to which defensins belong References External links