Molecular and cellular aspects of the serpinopathies and disorders in serpin activity

Serpins constitute a superfamily of proteins that possess a unique tertiary structure and mechanism of proteinase inhibition.

In humans, serpins constitute 10% of the plasma proteins and are best known as critical regulators of both the thrombotic and fibrinolytic systems.

Serpins also participate in the regulation of the complement cascade, angiogenesis, tumor metastasis, apoptosis and innate immunity.

Considering the importance of these molecules in regulating proteolytic cascades, it is not surprising to find that loss- and gain-of-function mutations result in significant human diseases.Massive thrombosis or bleeding, hereditary angioedema, Alzheimer's disease, diabetic angiopathy and tumor invasion are some of the human diseases associated with serpins.

In addition, mutations that alter serpin conformations (the serpinopathies) lead to lung disease, cirrhosis and a form of familial dementia.

The goal of this text is to present the current knowledge on the molecular and cellular basis of serpins and their diseases.Sample Chapter(s)Chapter 1: Evolution and Classification of the Serpin Superfamily (549 KB)Contents:Overview of the Serpin Superfamily:Evolution and Classification of the Serpin Superfamily (J A Irving et al.)Serpin Conformations (M C Pearce et al.)Mechanisms of Serpin Inhibition (P G W Gettins)Lessons from Model Organisms:Mouse Serpins and Transgenic Studies (D J Askew et al.)New Lessons from Poxvirus Serpins (P C Turner et al.)Uterine Serpins (P J Hansen et al.)Plant Serpins (J Hejgaard & T H Roberts)Serpin Physiology and Pathophysiology:Serpins, Apoptosis and Other Aspects of Cell Death (F L Scott)Serpin-Protein and Receptor Interactions (T M Antalis & D K Strickland)Congenital Deficiencies and Serpinopathies:The Serpinopathies and Respiratory Disease (D A Lomas et al.)Regulation of Hemostasis by Heparin-Binding Serpins (F C Church et al.)Neuroserpin in Neurological Disease (M Yepes & D A Lawrence)and other papersReadership: Physicians, pulmonologists, geneticists, hematologists, oncologists, gastroenterologists, neurologists; biochemists, developmental biologists, neuroscientists; courses in protease activity and enzymology for graduates and advanced level undergraduates.