Sigma Proteins: Evolution of the Concept of Sigma Receptors
Overview
- Editors:
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Felix J. Kim
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Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, USA
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Gavril W. Pasternak
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Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, USA
- Provides an updated perspective on this rapidly evolving field undergoing changes in fundamental concepts of key importance to the discipline of pharmacology
- Emphasis is laid on the roles of sigma proteins in pathophysiology and on emergent therapeutic initiatives
- New investigators combined with more experienced investigators - as represented by the editors
About this book
Two sigma receptor subtypes have been proposed, sigma1 and 2. Much of our understanding of this system is based on biochemical and pharmacological characterization of the cloned sigma1 receptor subtype (Sigma1). It has become clear that sigma receptors are not canonical receptors. Sigma1 is highly conserved among mammalian species, however, it does not share significant homology with any other mammalian protein. Although a range of structurally diverse small molecules bind Sigma1 with high affinity, and it has been associated with a broad range of signaling systems, Sigma1 itself has no known signaling or enzymatic activity. The evolution of this field over nearly four decades has more recently led to a fundamental shift in the concept of “sigma receptors” to what may more accurately and generally be called sigma proteins. Largely based on traditional pharmacologic approaches, the Sigma1 protein has been associated with a broad range of signaling systems, including G-protein coupled receptors, NMDA receptors, and ion channels. Sigma proteins have been linked to a range of physiological processes, including intracellular calcium signaling, neuroprotection, learning, memory, and cognition. Emerging genetic, clinical, and mechanism focused molecular pharmacology data demonstrate the involvement of proteins in a range of pathophysiologies and disorders including neurodegenerative disease, pain, addiction, psychomotor stimulant abuse, and cancer. However, an understanding of the physiological role of sigma proteins has remained elusive. Emerging data associate Sigma1 with chaperone-like activities or molecular scaffold functions. This book aims to provide an updated perspective on this rapidly evolving field undergoing changes in fundamental concepts of key importance to the discipline of pharmacology. It focusses on the reported roles of sigma proteins in pathophysiology and on emergent therapeutic initiatives.
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Table of contents (12 chapters)
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Front Matter
Pages i-viii
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- Erik Laurini, Domenico Marson, Maurizio Fermeglia, Sabrina Pricl
Pages 27-50
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- Frauke Weber, Bernhard Wünsch
Pages 51-79
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- Tangui Maurice, Nino Goguadze
Pages 81-108
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- Manuel Merlos, Luz Romero, Daniel Zamanillo, Carlos Plata-Salamán, José Miguel Vela
Pages 131-161
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- Jonathan L. Katz, Takato Hiranita, Weimin C. Hong, Martin O. Job, Christopher R. McCurdy
Pages 177-218
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- Valentina Sabino, Pietro Cottone
Pages 219-236
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- Felix J. Kim, Christina M. Maher
Pages 237-308
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- Chenbo Zeng, Elizabeth S. McDonald, Robert H. Mach
Pages 309-330
Editors and Affiliations
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Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, USA
Felix J. Kim
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Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, USA
Gavril W. Pasternak
About the editors
Felix J Kim PhD, Drexel University, College of Medicine, Pharmacology and Physiology, Philadelphia, USA
Gavril Pasternak MD Ph., Memorial Sloan-Kettering Cancer Center, Anne Burnett Tandy Chair in Neurology, Molec Pharmacology and Chemistry, New York, USA