AMYLOIDOSIS MECHANISMS AND PROSPECTS FOR THERAPY ppt

AMYLOIDOSIS - MECHANISMS AND PROSPECTS FOR THERAPY Edited by Svetlana Sarantseva Amyloidosis - Mechanisms and Prospects for Therapy Edited by Svetlana Sarantseva Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access articles distributed under the Creative Commons Non Commercial Share Alike Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published articles. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Petra Zobic Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright pix2go, 2011. Used under license from Shutterstock.com First published September, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Amyloidosis - Mechanisms and Prospects for Therapy, Edited by Svetlana Sarantseva p. cm. 978-953-307-253-1 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Chapter 1 Current and New Perspectives on the Molecular and Cellular Mechanisms of Amyloid Formation and Toxicity in Light Chain Amyloidosis 1 Ara Celi Di Costanzo and Marina Ramirez-Alvarado Chapter 2 Amyloid A Amyloidosis Secondary to Rheumatoid Arthritis 23 Tadashi Nakamura Chapter 3 Diagnosis and Treatment of AA Amyloidosis with Rheumatoid Arthritis: State of the Art 43 Takeshi Kuroda, Yoko Wada and Masaaki Nakano Chapter 4 Apolipoprotein A-I Associated Amyloidoses: The Intriguing Case of a Natively Unfolded Protein Fragment 63 Daria Maria Monti, Renata Piccoli and Angela Arciello Chapter 5 Interaction and Aggregation of Amyloid  Peptide with Multivalent Sulfonated Sugar 85 Yoshiko Miura and Tomohiro Fukuda Chapter 6 Laboratory Methods for the Diagnosis of Hereditary Amyloidoses 101 S. Michelle Shiller, Ahmet Dogan and W. Edward Highsmith, Jr. Chapter 7 Electron Microscopy in the Diagnosis of Amyloidosis 121 Tosoni A., Barbiano di Belgiojoso G. and Nebuloni M. Chapter 8 Amyloidosis in Domestic Animals: Pathology, Pathogenesis, Gross and Microscopic Lesions and Clinical Findings 149 Moges Woldemeskel VI Contents Chapter 9 Mouse Models to Study Systemic Amyloidoses: Is Prion-Like Transmission a Common Pathogenic Mechanism? 163 Keiichi Higuchi, Xiaoying Fu, Pengyao Zhang, Jinko Sawashita, Beiru Zhang, Jinze Qian, Wang Yaoyong and Masayuki Mori Chapter 10 Transthyretin Amyloidosis in Aged Vervet Monkeys, as a Candidate for the Spontaneous Animal Model of Senile Systemic Amyloidosis 181 Shinichiro Nakamura, Mitsuharu Ueda, Naohide Ageyama, Yukio Ando and Ryuzo Torii Chapter 11 Amyloidosis Associated to Leishmania Infection in Murine Model 191 Ana Lucia Abreu-Silva, Gabriel Xavier-Silva, Marlise Neves Milhomem, Mylena Andrea Oliveira Torres and Kátia da Silva Calabrese Chapter 12 Modeling Amyloid Diseases in Fruit Fly Drosophila Melanogaster 199 Svetlana Sarantseva and Alexander Schwarzman Preface Amyloidoses are a heterogeneous group of diverse etiology diseases. They are characterized by an endogenous production of abnormal proteins called amyloid proteins, which are not hydrosoluble, form depots in various organs and tissue of animals and humans and cause dysfunctions. Twenty-seven such proteins have been identified as amyloid precursors in humans. However, the answer why these proteins form aggregates and cause disease is not still completely clear. At present, there is not an effective treatment to prevent protein misfolding in these amyloid diseases. The aim of this book is to present an overview of different aspects of amyloidoses from basic mechanisms and diagnosis to latest advancements in treatment. Chapters 1 to 3 provide description and clinical features as well as molecular and cellular mechanisms, and current strategies for treatment of AL amyloidosis and AA amyloidosis with rheumatoid arthritis. The next two chapters are focused on molecular mechanisms of amyloid formation. Chapter 4 elucidates influence of intrinsic and extrinsic factors on fibril deposition in Apolipoprotein A-I associated amyloidoses with particular emphasis on the role of the pathogenic polypeptide named [1–93]ApoA-I. Chapter 5 examines the role of synthetic glycopolymers mimicing glycosaminoglycans in aggregation of amyloid β-peptide, which is shown to play central role in the pathogenesis of Alzheimer’s disease. Chapters 6 and 7 provide current methods for diagnosis and amyloid typing. More details are discussed on the advantages and limitations of the electron microscopy in the diagnosis of amyloidosis, particularly in early stage of disease. Chapter 8 covers the pathogenesis, lesions and clinical syndromes encompassing various forms of amyloidosis in animals. Finally, Chapters 9 to 12 are focused on creating models of human amyloidosis in animals. Indeed, some animal models accurately reproduce one or several characteristics of the pathogenesis of amyloid diseases and could be useful for understanding the molecular and cellular mechanisms of amyloid formation and developing novel therapeutic strategies. Several animal models are presented in the final chapters of this book. X Preface I would like to thank all the authors who have contributed to this book and I hope that this book will provide useful resource in study of amyloid disease pathogenesis and discovery of new therapeutic methods in the future. Svetlana Sarantseva Petersburg Nuclear Physics Institute, Russian Academy of Sciences Russia [...]... fold with 9 strands (A, B, C, C’, C”, D, E, F, and G) packed tightly against each other in two antiparallel  sheets joined together by a disulfide bridge in a form of a Greek key -barrel The N- and C- termini strands (A and G, respectively) are parallel (Branden & Tooze, 1999) The CDRs 2 Amyloidosis – Mechanisms and Prospects for Therapy form three loops between amino acids 24-34, 50-56 and 89-95 that... mutant 6 Amyloidosis – Mechanisms and Prospects for Therapy was less stable than wild-type LEN because Pro40 (very favorable for loops and turns) is conserved among 98% of all  and  germline sequences In vitro fibril formation studies have revealed that AL proteins form fibrils under a variety of solution conditions with varying kinetics and morphology of fibrils AL-09 is unique because it forms amyloid... than Wil, an 4 Amyloidosis – Mechanisms and Prospects for Therapy amyloidogenic protein from that germline with 11 somatic mutations (Del Pozo Yauner et al., 2008) The 6a germline also had significantly slower fibril formation kinetics than Wil When compared to AL-09 and I O18/O8, Wil and 6a demonstrated a comparable increase in stability, but faster fibril formation kinetics (14 hours for 6a compared... 283,45: 30950-6 Baden, E M., Sikkink, L A and Ramirez-Alvarado, M (2009) Light chain amyloidosis current findings and future prospects Curr Protein Pept Sci 10,5: 500-8 Current and New Perspectives on the Molecular and Cellular Mechanisms of Amyloid Formation and Toxicity in Light Chain Amyloidosis 17 Berghoff, M., Kathpal, M., Khan, F., Skinner, M., Falk, R and Freeman, R (2003) Endothelial dysfunction... and Seldin, D C., Eds (2007) XIth International Symposium on Amyloidosis Boca Raton, FL, CRC Press Taylor and Francis Group Current and New Perspectives on the Molecular and Cellular Mechanisms of Amyloid Formation and Toxicity in Light Chain Amyloidosis 21 Solomon, A., Weiss, D T and Wall, J S (2003) Immunotherapy in systemic primary (AL) amyloidosis using amyloid-reactive monoclonal antibodies Cancer... infections, and occasionally malignant neoplasias In Western countries, the most frequent predisposing conditions are rheumatic diseases AA 24 Amyloidosis – Mechanisms and Prospects for Therapy amyloidosis complicates about 6 % in patients with RA, although the reasons why the incidence is lower in the United States than in Europe and Japan are not clear Tuberculosis and leprosy are important causes of AA amyloidosis. .. understand the mechanism of AL fibril formation and the role of co-factors and the cellular environment on amyloidogenicity It is important to expand on the currently reported work with additional AL proteins to find commonalities and differences of fibril formation properties for the different AL proteins 3 Tissue damage in AL amyloidosis- toxic effect of light chains The most important aspect of AL amyloidosis. .. extracellular amyloidoses should allow more Current and New Perspectives on the Molecular and Cellular Mechanisms of Amyloid Formation and Toxicity in Light Chain Amyloidosis 15 precise understanding of the pathogenesis and the role of other proteins in facilitating or inhibiting amyloid generation and deposition The use of worms (Caenorhabditis elegans) and flies (Drosophila melanogaster) to study amyloidoses... destabilized half as much as AL-09 I Y87H also had intermediate fibril formation kinetics between those measured for I O18/O8 and AL-09, indicating that this mutation alone may not have been sufficient for the Current and New Perspectives on the Molecular and Cellular Mechanisms of Amyloid Formation and Toxicity in Light Chain Amyloidosis 7 amyloidogenicity observed in AL-09 However, introducing a... were the same, and the rate of fibril formation for JtoD29A was the same as that for Jto However, fibril formation kinetics were much faster for JtoR68S, and an X-ray crystal structure of this mutant revealed several side-chain differences compared to Jto and JtoD29A These differences changed the electrostatic potential surface and increased the amount of solvent-exposed hydrophobic surface for the protein . AMYLOIDOSIS - MECHANISMS AND PROSPECTS FOR THERAPY Edited by Svetlana Sarantseva Amyloidosis - Mechanisms and Prospects for Therapy Edited by. strands (A and G, respectively) are parallel (Branden & Tooze, 1999). The CDRs Amyloidosis – Mechanisms and Prospects for Therapy 2 form three loops between amino acids 24-34, 50-56 and. Amyloidosis – Mechanisms and Prospects for Therapy 6 was less stable than wild-type LEN because Pro40 (very favorable for loops and turns) is conserved among 98% of all  and  germline