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Advances in Experimental Medicine and Biology 964 Sylvia B. Smith Tsung-Ping Su Editors Sigma Receptors: Their Role in Disease and as Therapeutic Targets Advances in Experimental Medicine and Biology Volume 964 Editorial Board IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel N.S. ABEL LAJTHA, Kline Institute for Psychiatric Research, Orangeburg, NY, USA JOHN D. LAMBRIS, University of Pennsylvania, Philadelphia, PA, USA RODOLFO PAOLETTI, University of Milan, Milan, Italy More information about this series at http://www.springer.com/series/5584 Sylvia B. Smith • Tsung-Ping Su Editors Sigma Receptors: Their Role in Disease and as Therapeutic Targets Editor Sylvia B. Smith Tsung-Ping Su Departments of Cellular Biology Cellular Pathobiology Section, and Anatomy and Ophthalmology Integrative Neuroscience Research and the James and Jean Culver Vision Branch, Intramural Research Program Discovery Institute National Institute on Drug Abuse, Medical College of Georgia National Institutes of Health, at Augusta University US Department of Health Augusta, GA, USA and Human Services Baltimore, MD, USA ISSN 0065-2598 ISSN 2214-8019 (electronic) Advances in Experimental Medicine and Biology ISBN 978-3-319-50172-7 ISBN 978-3-319-50174-1 (eBook) DOI 10.1007/978-3-319-50174-1 Library of Congress Control Number: 2016961509 © Springer International Publishing AG (outside the USA) 2017 This book was created within the capacity of an US governmental employment. US copyright protection does not apply. This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface In 2007, a book entitled Sigma Receptors: Chemistry, Cell Biology and Clinical Implications was published by Springer (Neuroscience Division) with Drs. R. Matsumoto, W. Bowen, and T. Su as editors. Since that time, the field of study regarding sigma receptors has exploded. Indeed in 2006 (at the time the last book would have been updated), there were ~1200 papers pub- lished about sigma receptor; by late 2016, there were more than 4000 publi- cations. The significant progress in the field necessitated a compendium focused on the role of sigma receptors in disease and their potential role as therapeutic targets. Originally confused with opioid receptors and then orphan receptors with no biological function, sigma-1 receptor is now recognized as relevant to many degenerative diseases with remarkable potential as a therapeutic target. In this text, new information about the crystal structure of sigma-1 receptor and its binding sites are provided as well as its expression in many cell types. Its putative role in degenerative neuronal diseases including amyotrophic lat- eral sclerosis, Alzheimer’s disease, Parkinson’s disease, pain, drug addiction, and locomotor activity is described. Its role in cancer biology and its promis- ing potential in treatment of blinding visual diseases emphasize the tremen- dous far-reaching potential for ligands for these receptors. There has been progress in our understanding of sigma-2 receptor, which is covered in this text as well. Exciting breakthroughs in the dynamic field of sigma receptor biology in the last decade are reported herein, which we hope will guide future investi- gators in determining the full potential of this unique, yet abundantly, expressed protein. We thank the many investigators who contributed to this work and look forward to continuing discoveries as the field of sigma recep- tor biology unfolds. We are grateful to Dr. Meran Owen, Senior Publishing Editor at Springer, for reaching out to us and suggesting the need for this updated volume. We appreciate the efforts of Tanja Koppejan, who oversaw the publishing of this work. We acknowledge with gratitude the capable support of Mrs. Heide Andrews for her assistance in editing the volume. Augusta, GA, USA Sylvia B. Smith Baltimore, MD, USA Tsung-Ping Su v Contents 1 Introduction to Sigma Receptors: Their Role in Disease and as Therapeutic Targets ....................................... 1 Sylvia B. Smith 2 Structural Perspectives on Sigma-1 Receptor Function ........................................................................ 5 Assaf Alon, Hayden Schmidt, Sanduo Zheng, and Andrew C. Kruse 3 A Review of the Human Sigma-1 Receptor Structure .............. 15 Felipe Ossa, Jason R. Schnell, and José Luis Ortega-Roldan 4 Fluorinated PET Tracers for Molecular Imaging of σ Receptors in the Central Nervous System ......................... 31 1 Frauke Weber, Peter Brust, Erik Laurini, Sabrina Pricl, and Bernhard Wünsch 5 The Evolution of the Sigma-2 (σ) Receptor from 2 Obscure Binding Site to Bona Fide Therapeutic Target ........... 49 Chenbo Zeng and Robert H. Mach 6 Sigma 1 Receptor and Ion Channel Dynamics in Cancer ..................................................................... 63 Olivier Soriani and Raphaël Rapetti-Mauss 7 Sigma-1 Receptors Fine-Tune the Neuronal Networks ............ 79 Shang-Yi Anne Tsai and Tsung-Ping Su 8 Pharmacological Modulation of the Sigma 1 Receptor and the Treatment of Pain ........................................................... 85 Manuel Merlos, Javier Burgueño, Enrique Portillo- Salido, Carlos Ramón Plata-Salamán, and José Miguel Vela 9 Sigma-1 Receptor Antagonists: A New Class of Neuromodulatory Analgesics .................................................. 109 Cristina Sánchez-Fernández, José Manuel Entrena, José Manuel Baeyens, and Enrique José Cobos vii viii Contents 10 S igma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection .............................. 133 Linda Nguyen, Brandon P. Lucke-Wold, Shona Mookerjee, Nidhi Kaushal, and Rae R. Matsumoto 11 S igma-1 Receptor Agonists and Their Clinical Implications in Neuropsychiatric Disorders .............................. 153 Yakup Albayrak and Kenji Hashimoto 12 R ole of Sigma-1 Receptor in Cocaine Abuse and Neurodegenerative Disease .................................................. 163 Yu Cai, Lu Yang, Fang Niu, Ke Liao, and Shilpa Buch 13 Sigma Receptors and Substance Use Disorders ........................ 177 Valentina Sabino, Callum Hicks, and Pietro Cottone 14 S timulation of the Sigma-1 Receptor and the Effects on Neurogenesis and Depressive Behaviors in Mice ................. 201 Kohji Fukunaga and Shigeki Moriguchi 15 R ole of σ1 Receptors in Learning and Memory and Alzheimer’s Disease-Type Dementia ................................... 213 Tangui Maurice and Nino Goguadze 16 Sigma-1 Receptor in Motoneuron Disease ................................. 235 Renzo Mancuso and Xavier Navarro 17 The Sigma-1 Receptor–A Therapeutic Target for the Treatment of ALS? ........................................................... 255 Timur A. Mavlyutov, Erin M. Baker, Tasher M. Losenegger, Jaimie R. Kim, Brian Torres, Miles L. Epstein, and Arnold E. Ruoho 18 The Role of Sigma1R in Mammalian Retina ............................. 267 Jing Wang, Xuezhi Cui, Penny Roon, Alan Saul, and Sylvia B. Smith 19 Peeking into Sigma-1 Receptor Functions Through the Retina ...................................................................... 285 Timur A. Mavlyutov and Lian-Wang Guo 20 The Role of Sigma 1 Receptor as a Neuroprotective Target in Glaucoma...................................................................... 299 Barbara Mysona, Neil Kansara, Jing Zhao, and Kathryn Bollinger Index ...................................................................................................... 309 Contributors Yakup Albayrak Namik Kemal University, Tekirdag, Turkey Assaf Alon Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA José Manuel Baeyens Department of Pharmacology, School of Medicine, University of Granada, Granada, Spain Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain Erin M. Baker Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA Kathryn Bollinger Department of Ophthalmology, Medical College of Georgia at Augusta University, Augusta, GA, USA Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA, USA Medical College of Georgia at Augusta University, Augusta, GA, USA The James and Jean Culver Vision Discovery Institute, Augusta, GA, USA Peter Brust Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Leipzig, Germany Shilpa Buch Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA Javier Burgueño Drug Discovery and Preclinical Development, ESTEVE. Parc Científic de Barcelona, Barcelona, Spain Yu Cai Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA Enrique José Cobos Department of Pharmacology, School of Medicine, University of Granada, Granada, Spain Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain Teófilo Hernando Institute for Drug Discovery, Madrid, Spain ix x Contributors Pietro Cottone Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA Xuezhi Cui Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA The James and Jean Culver Vision Discovery Institute, Augusta University, Augusta, GA, USA José Manuel Entrena Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain Animal Behavior Research Unit, Scientific Instrumentation Center, University of Granada, Granada, Spain Miles L. Epstein Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA Kohji Fukunaga Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan Nino Goguadze INSERM U1198, University of Montpellier, Montpellier, France Institute of Chemical Biology, Ilia State University, Tbilisi, GA, USA Lian-Wang Guo Department of Surgery and McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, 5151 Wisconsin Institute for Medical Research, Madison, WI, USA Kenji Hashimoto Chiba University, Chiba, Japan Callum Hicks Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA Neil Kansara Department of Ophthalmology, Medical College of Georgia at Augusta University, Augusta, GA, USA The James and Jean Culver Vision Discovery Institute, Augusta, GA, USA Nidhi Kaushal Takeda California, Inc., San Diego, CA, USA Jaimie R. Kim Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA Andrew C. Kruse Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA Erik Laurini Molecular Simulations Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), University of Trieste, Trieste, Italy Ke Liao Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA Tasher M. Losenegger Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA

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Originally confused with opioid receptors and then orphan receptors with no biological function, Sigma Receptors are now recognized as relevant to many degenerative diseases with remarkable potential as therapeutic targets. In this text, new information about the structure of sigma 1 receptor, its b
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