Title: Transglutaminases as Targets for Pharmacological Inhibition
Volume: 5
Issue: 3
Author(s): Jolanta M. Wodzinska
Affiliation:
Keywords:
transglutaminase, factor xiii, thrombosis, neurodegenerative disease, celiac disease, inflammation, fibrosis and inhibitor
Abstract: Transglutaminases (TGases), a family of enzymes that catalyze the formation of ε-(γ-glutamyl)lysine isopeptide linkage, play an important physiological role in hemostasis, wound healing, assembly and remodeling of the extracellular matrix, cell signaling and apoptosis. Although many members of this class of enzymes have been known for decades, their role in various physiological and pathological processes is still a subject of substantial research and debate. Convincing evidence exists that TGases are involved in formation of cytotoxic proteinatious aggregates in Alzheimers, Huntingtons and other neurodegenerative diseases. However, it is not clear if elevated levels of TGases play a causative or protective role in several of these processes. Increased or defective TGase activity is a factor in cortical cataract formation, lamellar ichtyosis and fibrosis. TGase creates epitopes for the production of autoantibodies in celiac disease and possibly other autoimmune diseases. Another TGase, Factor XIIIa, is involved in the etiology of vascular diseases. Modulation of TGase activity through its selective inhibition may have therapeutic benefit in a wide variety of diseases. This paper will examine TGases as targets for the development of new therapeutics and review the progress in discovery of selective inhibitors of these enzymes.
