Thiol protease is a kind of proteolytic enzyme. Thiol protease catalyzes hydrolysis of peptide bond by sulfhydryl group with sulfhydryl group in the active center. Interestingly, thiol proteases, also known as cysteine proteases, are hydrolase enzymes that degrade proteins. Moreover, Cathepsin is the main member of the cysteine protease family. Specifically, Cathepsin is a kind of target protease that has attracted much attention in recent years. It is a group of proteases found in the cells of various animal tissues. Cathepsin also includes peptide-chain endopeptidases Cathepsin B, H, L. Surprisingly, Cathepsin is present in lysosomes. Undoubtedly, autophagosome formation is often followed by a fusion of the autophagosome with the endosome, creating an intermediate compartment, the amphisome.
Here, we focus on the thiol protease inhibitor, Leupeptin.
Leupeptin is an orally active and membrane-permeable thiol protease inhibitor. Notably, Leupeptin inhibits Cathepsin B, Cathepsin H and Cathepsin L, and also impairs amphisome-lysosome fusion. Furthermore, Leupeptin also exhibits anti-inflammatory effect. It is worth noting that, People first identifies Leupeptin in the culture filtrates of various actinomycetes. Perhaps, organisms which produce a protease produce at the same time an inhibitor to protect themselves from the emzymatic effect. In vivo, Leupeptin produces a strong, dose-dependent increase in LC3b-II in both the total tissue extracts and the lysosome and autophagosome-enriched pellet fraction. Extraordinary, Jeffrey et al. found that the rate of LC3b accumulation after Leupeptin treatment was greatest in the liver and lowest in spleen in 2011.
Taken together, Leupeptin, as a thiol protease inhibitor, impairs amphisome-lysosome fusion. Leupeptin is a potent compound of inflammation disease.