Clinical Potential of Agents That Affect Thrombin Signaling in Degenerative and Traumatic Neurologic Disorders

Historically, thrombin has been a favorite enzyme protease to study because of its activity towards large substrates, particularly those that are zymogens for other enzymes involved in coagulation. The most well known, in this context, is Factor XIII activation to XIIIa. Thrombin catalyzes this reaction, activating a powerful Ca2+-dependent enzyme for crosslinking fibrin via the γ-carboxamide group of glutamine residues and the e-amino group of lysine. However, in order for Factor XIIIa to utilize the fibrin substrate, this molecule must result from specific and selective cleavage by thrombin of the plasma protein, fibrinogen (Fenton, 1986; Fenton et al., 1993).