Mechanisms of serpin dysfunction in disease

Abstract

The serpin superfamily encompasses hundreds of proteins, spread across all kingdoms of life, linked by a common tertiary fold. This review focuses on five diseases caused by serpin dysfunction: variants of antithrombin III lose their ability to interact with heparin; the alpha1-antitrypsin Pittsburgh mutation causes a change in target proteinase; the alpha1-antitrypsin Z mutation and neuroserpin, polymerisation of which lead to cellular cytotoxicity; and a loss of maspin expression resulting in cancer.