Proprotein convertases as therapeutic targets

Background: Limited endoproteolysis of precursor proteins is a common mechanism of production of functional proteins and peptides. In the secretory pathway of eukaryotic cells, this endoproteolysis is principally mediated by a family of calcium-dependent serine proteases, generically known as proprotein convertases. Altered expression of these enzymes in experimental animal models and in humans has been associated with numerous pathologies, including infertility, developmental defects, metabolic dysfunctions, cancer, cardiovascular diseases and infectious diseases. Objective: To review experimental evidence of the therapeutic potential of proprotein convertase inhibitors or silencers. Conclusions: Several potent inhibitors have been developed and successfully tested. Their therapeutic use must await further improvements in potency, selectivity, cellular delivery and tissue targeting.