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.

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 binding sites are provided as well as its expression in many cell types. It’s putative role in degenerative neuronal diseases including amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, pain, drug addiction and locomotor activity. Their roles in possible treatments for blinding retinal diseases emphasize the tremendous far-reaching potential for ligands for these receptors. Exciting breakthroughs in this dynamic field in the last decade are reported herein, which will guide future investigators in determining the full potential of this unique, yet abundantly expressed protein.

This book provides an update on sigma receptors, and summarizes recent advances in the medicinal chemistry, molecular biology, and cell biology of sigma receptors. It describes the functional effects mediated by these receptors and the potential clinical implications of these actions. The information is put in a historical perspective. This provides a launching point from which future studies and research directions can easily be developed.

Lipids are the most abundant organic compounds found in the brain, accounting for up to 50% of its dry weight. The brain lipidome includes several thousands of distinct biochemical structures whose expression may greatly vary according to age, gender, brain region, cell type, as well as subcellular localization. In synaptic membranes, brain lipids specifically interact with neurotransmitter receptors and control their activity. Moreover, brain lipids play a key role in the generation and neurotoxicity of amyloidogenic proteins involved in the pathophysiology of neurological diseases. The aim of this book is to provide for the first time a comprehensive overview of brain lipid structures, and to explain the roles of these lipids in synaptic function, and in neurodegenerative diseases, including Alzheimer's, Creutzfeldt-Jakob's and Parkinson's. To conclude the book, the authors present new ideas that can drive innovative therapeutic strategies based on the knowledge of the role of lipids in brain disorders. - Written to provide a "hands-on" approach for readers - Biochemical structures explained with molecular models, and molecular mechanisms explained with simple drawings - Step-by-step guide to memorize and draw lipid structures - Each chapter features a content summary, up-to-date references for additional study, and a key experiment with an explanation of the technique

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This volume contains a unique selection of chapters covering a wealth of contemporary topics in this ubiquitous and diverse system of cell signaling. It offers much more than the accessibility and authority of a primary text book, exploring topics ranging from the fundamental aspects of calcium signaling to its varied clinical implications. It presents comprehensive discussion of cutting-edge research alongside detailed analysis of critical issues, at the same time as setting out testable hypotheses that point the way to future scientific endeavors. The contributions feature material on theoretical and methodological topics as well as related subjects including mathematical modeling and simulations. They examine calcium signaling in a host of contexts, from mammalian cells to bacteria, fruit fly and zebrafish. With much of interest to newcomers to the field as well as seasoned experts, this new publication is both wide-ranging and authoritative. The chapter “Calcium Signaling: From Basic to Bedside” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.