Proteases, Protease Inhibitors and Protease-Derived Peptides : Importance in Human Pathophysiology and Therapeutics

Proteases, Protease-Derived Peptides and Protease Inhibitors Many physiological as weil as pathophysiological processes are mediated by proteases and the products of their actions, protease-derived peptides. However, the uncontrolled activity of proteases can be extraordinarily destructive and dangerous to normal biologie systems. As a result, biology has gone to great lengths to control the activities of the proteases involved in these systems by developing aseries of both highly specific (regulatory) and non-specific (protective) anti-proteases. The protease/anti-protease balancing activities include the normal homeostatic processes of clotting and clot lysis, hormonal regulation of blood pressure and the control of the inflammatory response represented by both the humoral (the kallikrein-kinin and complement systems) and cellular (neutrophil and macrophage derived proteases) components of the inflammation. Examples of successful therapies directed at these protease dependent systems include the use of warfarin and heparin to control thrombosis and streptokinase or tissue plasminogen activator (tPA) for the acceleration of clot dissolution. Similarly, the use of angiotensin converting enzyme (ACE, a type of limited activity protease or peptidase) inhibitors has made a significant impact on the treatment of hypertension. Lastly, the restitution of normal antiprotease levels by the infusion of the purified protein in patients with genetic alpha-1-antiprotease deficiency is regularly being used to reduce the rate of lung function 1055 caused by the unopposed activity of human neutrophil elastase in these individuals.