| The regulation of protein secretion is central to the proper functioning of eukaryotic organisms. One mode of protein secretion is the generation of soluble fragments of membrane-bound proteins by limited proteolysis through the action of proteases termed secretases, or sheddases. In general, cleavage occurs close to the extracellular face of the membrane, releasing active protein. Proteins secreted in this fashion include some membrane receptors and receptor ligands, ectoenzymes and cell adhesion molecules. Since the proteins concerned are involved in pathophysiological processes, such as neurodegeneration, inflammation and oncogenesis, inhibitors of respective secretases are emerging as promising therapeutic drugs. This article will review a number of methods that have allowed molecular cloning of secretases and discuss different approaches to discovering specific secretase inhibitors. |
