Proteins are essential macromolecules of living organisms. They are continuously being degraded into their constituent amino acids which can be reused in the synthesis of new proteins. Every cellular protein has its own half-life time. In humans, for instance, 50% of the liver and plasma proteins are replaced in 10 days, whereas in muscles it takes 180 days. In average, every 80 days about 50% of our proteins are totally replaced. Although the regulation of protein degradation is as important as their synthesis to keep each cell protein concentration at the optimum level, research in this area remained until the end of the 1970s. Up to this time, lysosomes, discovered in the 1950s by the Belgian cytologist Christian de Duve, were thought responsible for the complete digestion of intra- and extracellular proteins by the lysosomal hydrolytic enzymes.
Between the 1970s and 1980s, this view drastically changed. New experimental evidences showed that, under physiological conditions, non-lysosomal proteases were responsible for limited proteolysis of intra- and/or extracellular proteins, a concept originally conceived by Linderstᴓm-Lang in 1950. Endogenous or exogenous proteins are processed by non-lysosomal proteases into intermediate-sized polypeptides, which display gene and metabolic regulation, neurologic, endocrine, and immunological roles, whose dysfunction might explain a number of pathologies. Consequently, protein degradation did not represent anymore the end of the biological function of proteins, but rather the beginning of a yet unexplored side of the biology of the cells. A number of intra- or extracellular proteases release protein fragments endowed with essential biological activities. These hydrolytic processes could be carried out by proteases such as Proteasomes, Proprotein Convertases, Caspases, Rennin and Kallikreins. Among the products released by the non-lysosomal proteases are the bioactive oligopeptides such as hormones, neuropeptides and epitopes that, once released, could be modulated in their biological activities by specific peptidases, which promote the trimming, conversion and/or inactivation of the bioactive oligopeptides.