TY - JOUR JF - iums-ijpt JO - 3 VL - 1 IS - 2 PY - 2002 Y1 - 2002/11/01 TI - NEP, ACE and Homologues: The Pathophysiology of Membrane Metalloproteases TT - N2 - The zinc metalloprotease, neprilysin (NEP), plays a role in the metabolism of cardiovascular, inflammatory and neuropeptides, including mitogenic peptides such as bombesin. In the cardiovascular system, NEP has a primary role in the inactivation of natriuretic peptides but also contributes to local metabolism of angiotensin, endothelins and bradykinin. Hence NEP is seen as a potential therapeutic target and drug development is facilitated by its recent structural solution. In prostate cancer, NEP is dramatically down-regulated allowing mitogenic peptides to drive androgen-independent progression of the disease. NEP also contributes to the catabolism of the neurotoxic beta-amyloid peptide in Alzheimer’s disease. Thus up- or downregulation of NEP activity critically affects peptide metabolism and can contribute to the pathophysiology of a number of diseases. The human genome contains seven NEP-like enzymes, including the endothelin converting enzymes (ECE) and aspects of their physiology and properties will be highlighted. We have also identified a novel human homologue of the zinc metalloprotease, angiotensin converting enzyme (ACE). This enzyme (ACEH) hydrolyses angiotensins I and II but not bradykinin and functions exclusively as a carboxypeptidase. Its localization and possible roles in regulation of the renin-angiotensin and other peptide systems will be described and compared with those of ACE itself. SP - 30 EP - 0 AU - Turner, A.J. AD - UR - http://ijpt.iums.ac.ir/article-1-15-en.html ER -