Molecular and Cellular Aspects of the Serpinopathies and Disorders in Serpin Activity

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Overview

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.

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Product Details

  • ISBN-13: 9789812569639
  • Publisher: World Scientific Publishing Company, Incorporated
  • Publication date: 2/28/2007
  • Pages: 672
  • Product dimensions: 6.20 (w) x 9.10 (h) x 1.30 (d)

Table of Contents

Editors     ix
Contributors     xi
Serpinopathies Foreword     xxv
Serpinopathies Preface     xxvii
Overview of the Serpin Superfamily
Evolution and Classification of the Serpin Superfamily   James A. Irving   Lisa D. Cabrita   Dion Kaiserman   Margaret M. Worrall   James C. Whisstock     1
Serpin Conformations   Mary C. Pearce   Robert N. Pike   Arthur M. Lesk   Stephen P. Bottomley     35
Mechanisms of Serpin Inhibition   Peter G. W. Gettins     67
Lessons from Model Organisms
Mouse Serpins and Transgenic Studies   David J. Askew   Paul Coughlin   Phillip I. Bird     101
Serpins in Prokaryotes   Qingwei Zhang   Ruby Law   Ashley M. Buckle   Lisa Cabrita   Sheena McGowan   James A. Irving   Noel G. Faux   Arthur M. Lesk   Stephen P. Bottomley   James C. Whisstock     131
New Lessons from Poxvirus Serpins   Peter C. Turner   Priscilla F. McAuliffe   Amy L. MacNeill   Richard W. Moyer     163
The Intracellular Serpins of Caenorhabditis elegans   Stephen C. Pak   Yuko S. Askew   Cliff J. Luke     195
Drosophila Serpins: Regulatory Cascades in Innate Immunity and Morphogenesis   David Gubb   Andrew Robertson   Tim Dafforn   Laurent Troxler   Jean-Marc Reichhart     207
Serpins in a Lepidopteran Insect, Manduca sexta   Michael R. Kanost     229
MENT, a Chromatin-Associated Serpin from Avian Blood Cells: Structure and Function   Sergei A. Grigoryev   Yaroslava A. Bulynko   Robert N. Pike   James C. Whisstock     243
Uterine Serpins   Peter J. Hansen   Saban Tekin   Maria B. Padua     261
Plant Serpins   Jorn Hejgaard   Thomas H. Roberts     279
Serpin Physiology and Pathophysiology
Serpins, Apoptosis and Other Aspects of Cell Death   Fiona L. Scott     301
Serpins in Malignancy: Tumor Cell Invasion, Motility and Angiogenesis   Philip A. Pemberton   Christian Schem   Nicolai Maass   Ming Zhang     337
Serpins in Malignancy: Prognostic Indicators   Hiroshi Kato   Yuko S. Askew   Shugo Nawata   Akihiro Murakami   Yoshinori Suminami   Gary Clayman     363
SERPINB7 (Megsin) Nephropathy   Toshio Miyata      383
Serpin-Protein and Receptor Interactions   Toni M. Antalis   Dudley K. Strickland     393
Serpins and the Metabolic Syndrome   Jun Wada     411
Serpin Interactions with Bacterial Peptidases   Jan Potempa   Tomasz Kantyka   Daniel Nelson     425
Congenital Deficiencies and Serpinopathies
The Serpinopathies and Respiratory Disease   David A. Lomas   Didier Belorgey   Elena Miranda   Meera Mallya   Peter Hagglof   Lynda K. Sharp   Russell L. Phillips   Richard Page   Mark J. Davies   Damian C. Crowther     445
Liver Disease in [alpha subscript 1]-Antitrypsin Deficiency   David H. Perlmutter     483
Regulation of Hemostasis by Heparin-Binding Serpins   Frank C. Church   Robert N. Pike   Douglas M. Tollefsen   Ashley M. Buckle   Angelina V. Ciaccia   Steven T. Olson     509
C1 Inhibitor: Structure, Function, Biologic Activity and Angioedema   Philip A. Patston   Alvin E. Davis III     555
Neuroserpin in Neurological Disease   Manuel Yepes   Daniel A. Lawrence     593
Serpins and Alzheimer's Disease   H. Tonie Wright   Sabina Janciauskiene     619
Index     635
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