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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 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.
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.
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.
The Latest Applications For Cellmechanism Research in Drug Discovery Designed to connect research on cell mechanisms with the drug discovery process, Therapeutic Targets: Modulation, Inhibition, and Activation introduces readers to a range of new concepts and novel approaches to drug screening and therapeutic drug targeting to help inform future avenues of drug research. Highly topical, this accessible edited volume features chapters contributed by respected experts from around the globe. The book helps postgraduate students and professional scientists working in academia and industry understand the molecular mechanisms of pharmacology, current pharmacological knowledge, and future perspectives in drug discovery, focusing on important biochemical protein targets and drug targeting strategies for specific diseases. Examining the pharmacology of therapeutically undefined targets and their potential applications, it includes chapters on traditional therapeutic targets, including enzymes (phosphodiesterases and proteases), ion channels, and G protein-coupled receptors, as well as more recently identified avenues of exploration, such as lipids, nuclear receptors, gene promoters, and more. Since different diseases require different targeting techniques, the book also includes dedicated chapters on strategies for investigating Alzheimer's, diabetes, pain, and inflammation treatments. Concluding with a cross-sectional look at new approaches in drug screening, Therapeutic Targets is an invaluable resource for understanding where the next generation of drugs are likely to emerge.
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
The Advances in Pharmacology series presents a variety of chapters from the best authors in the field. - Includes the authority and expertise of leading contributors in pharmacology - Presents the latest release in the Advances in Pharmacology series
Neurodegenerative diseases represent a very large group of heterogeneous disorders affecting specific subtypes of neurons in the brain. This book contributes insight both to the awareness of the brain and its neurodegenerative states. The chapters present current knowledge regarding genetics, molecular mechanisms, and new therapeutic strategies against neurodegenerative disorders. The book is intended to serve as a source to aid clinicians and researchers in the field, and also life science readers to increase their understanding and awareness of the clinical correlations, genetic aspects, neuropathological findings, and current therapeutic interventions in neurodegenerative diseases. I believe that this book will enlighten the curiosity for neurodegeneration and also encourage researchers to work on potentially effective molecular therapies for still mysterious neurodegenerative disorders.
Advances in anti-cancer chemotherapy over recent years have led to improved efficacy in curing or controlling many cancers. Some chemotherapy-related side-effects are well recognized and include: nausea, vomiting, bone marrow suppression, peripheral neuropathy, cardiac and skeletal muscle dysfunction and renal impairment. However, it is becoming clearer that some chemotherapy-related adverse effects may persist even in long term cancer survivors. Problems such as cognitive, cardiovascular and gastrointestinal dysfunction, and neuropathy may lead to substantial long term morbidity. Despite improvements in treatments to counteract acute chemotherapy-induced adverse effects, they are often incompletely effective. Furthermore, counter-measures for some acute side-effects and many potential longer term sequelae of anti-cancer chemotherapy have not been developed. Thus, new insights into prevalence and mechanisms of cancer chemotherapy-related side effects are needed and new approaches to improving tolerance and reduce sequelae of cancer chemotherapy are urgently needed. The present Research Topic focuses on adverse effects and sequelae of chemotherapy and strategies to counteract them.
Neurological disease affects nearly 25%–30% of the world’s population, exerting enormous financial strain on the healthcare system. Estimated current costs are around $800 annual billion, and this number is expected to increase exponentially as the global population ages. As such, new and alternative neuroprotective strategies are urgently needed. This book examines some of the most promising approaches in neuroprotection as well as discusses current goals and prospects. Organized into three sections, chapters cover such topics as the use of cannabinoids, medicinal plants, and essential oils in Alzheimer’s and Parkinson’s; protein misfolding and the neuroprotective potential of vitamin E in cerebral ischemia; and potential new neurological treatments and their mechanisms of action.