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In the decade before the publication of this study, melanocortin biology matured. Three additional receptors were discovered, and animal models were established addressing the function of each receptor. Researchers now know that the diverse physiologic responses to melanocortins - including their role in development, weight and endocrine regulation, cortisol production, secretion from exocrine glands, and pigmentation - can be defined in terms of individual receptors. In this text, contributors from the field of evolutionary biology, peptide chemistry, pigmentation biology, neuroscience, endocrinology and genetics provide the reader with a comprehensive review of melanocortin biology. Six areas of active research are addressed: peptide and small molecule chemistry; receptor structure and function; energy homeostasis; pigmentation; adrenocorticol function; and behaviour. There are 56 papers and 20 posters altogether, taken from the Fifth Melanocortin Meeting, held in 2002.
Obesity is an epidemic with enormous health, economic and social burdens. Current drugs for obesity treatment are far from ideal in terms of efficacy and side effects. Reviews in this volume of Progress in Molecular Biology and Translational Science summarize current status in studies of a number of G protein-coupled receptors that were shown to be promising targets for obesity treatments. Some of these receptors also cause monogenic obesity in humans. - Subject matter: obesity is an epidemic and G protein-coupled receptors are promising drug targets, with significant potential as new anti-obesity drugs - Chapters are written by leading experts
Roger Cone and a distinguished team of expert investigators provide the first major treatment of this critically important receptor family. The book illuminates the structure and function of these receptors through a wide-ranging review of the latest findings concerning the biology, physiology, and pharmacology of their peptide ligands and covers the major melanocortin peptides, Melanocortin-1-Receptors through Melanocortin-5-Receptors. Topics include the characterization of the melanocortin receptors, the biochemical mechanism of receptor action, and receptor function and regulation. Timely and authoritative, The Melanocortin Receptors offers an up-to-date knowledge base on the remarkably complex structure and functions of the melanocortins, a guide that will prove invaluable for today's neuroscientists, endocrinologists, pharmacologists, and other clinical and experimental investigators working in this fast moving field.
Neuroendocrinology underpins fundamental physiological, molecular, biological, and genetic principles such as the regulation of gene transcription and translation. This handbook highlights the experimental and technical foundations of each area's major concepts and principles.
This book is not going to be an exhaustive survey covering all aspects of rational drug design. Instead, it is going to provide critical know-how through real-world examples. Relevant case studies will be presented and analyzed to illustrate the following: how to optimize a lead compound whether one has high or low levels of structural information; how to derive hits from competitors' active compounds or from natural ligands of the targets; how to springboard from competitors' SAR knowledge in lead optimization; how to design a ligand to interfere with protein-protein interactions by correctly examining the PPI interface; how to circumvent IP blockage using data mining; how to construct and fully utilize a knowledge-based molecular descriptor system; how to build a reliable QSAR model by focusing on data quality and proper selection of molecular descriptors and statistical approaches. A Practical Guide to Rational Drug Design focuses on computational drug design, with only basic coverage of biology and chemistry issues, such as assay design, target validation and synthetic routes. - Discusses various tactics applicable to daily drug design - Readers can download the materials used in the book, including structures, scripts, raw data, protocols, and codes, making this book suitable resource for short courses or workshops - Offers a unique viewpoint on drug discovery research due to the author's cross-discipline education background - Explores the author's rich experiences in both pharmaceutical and academic settings
Advances in Peptide and Peptidomimetic Design Inspiring Basic Science and Drug Discovery is a book dedicated to Prof. Victor J. Hruby on the occasion of his 80th birthday. This book includes twenty contributions from authors representing diverse multidisciplinary fields of scientific expertise, and is focused on the extraordinary potential of peptides and peptidomimetics as a surging therapeutic modality and as tools for basic research and technology development.
The most comprehensive and integrated book on pigmentation The Pigmentary System, Second Edition, gathers into one convenient, all-inclusive volume a wealth of information about the science of pigmentation and all the common and rare clinical disorders that affect skin color. The two parts, physiology (science) and pathophysiology (clinical disorders), are complementary and annotated so that those reading one part can easily refer to relevant sections in the other. For the clinician interested in common or rare pigment disorders or the principles of teaching about such disorders, this book provides an immediate and complete resource on the biologic bases for these disorders. For the scientist studying the biology of melanocyte function, the book provides a list of disorders that are related to basic biological functions of melanocytes. New features of this Second Edition include: Completely new section on the basic science of pigmentation – explaining the integration of melanocyte functions with other epidermal cells and with various organ systems like the immune system New chapters on pigmentary disorders related to intestinal diseases, the malignant melanocyte, benign proliferations of melanocytes (nevi) and phototherapy with narrow band UV All clinical chapters include the latest genetic findings and advances in therapy More than 400 color images of virtually all clinical disorders The book is ideal for all dermatologists and especially those interested in disorders of pigmentation. It is of particular use for pediatric dermatologists and medical geneticists caring for patients with congenital and genetic pigmentary disorders. This authoritative volume will fill the gap for dermatology training programs that do not have local experts on pigmentation. Basic and cosmetic scientists studying pigmentation and melanocytes will find the science and clinical correlations very useful in showing human significance and relevance to the results of their studies.
By stimulating adrenal gland and corticosteroid synthesis, the adrenocorticotropic hormone (ACTH) plays a central role in response to stress. In this Research Topic, a particular attention has been given to the recent developments on adrenocortical zonation; the growth-promoting activities of ACTH; the various steps involved in acute and chronic regulation of steroid secretion by ACTH, including the effect of ACTH on circadian rhythms of glucocorticoid secretion. The Research Topic also reviews progress and challenges surrounding the properties of ACTH binding to the MC2 receptor (MC2R), including the importance of melanocortin-2 receptor accessory protein (MRAP) in MC2R expression and function, the various intracellular signaling cascades, which involve not only protein kinase A, the key mediator of ACTH action, but also phosphatases, phosphodiesterases, ion channels and the cytoskeleton. The importance of the proteins involved in the cell detoxification is also considered, in particular the effect that ACTH has on protection against reactive oxygen species generated during steroidogenesis. The impact of the cellular microenvironment, including local production of ACTH is discussed, both as an important factor in the maintenance of homeostasis, but also in pathological situations, such as severe inflammation. Finally, the Research Topic reviews the role that the pituitary-adrenal axis may have in the development of metabolic disorders. In addition to mutations or alterations of expression of genes encoding components of the steroidogenesis and signaling pathways, chronic stress and sleep disturbance are both associated with hyperactivity of the adrenal gland. A resulting effect is increased glucocorticoid secretion inducing food intake and weight gain, which, in turn, leads to insulin and leptin resistance. These aspects are described in detail in this Research Topic by key investigators in the field. Many of the aspects addressed in this Research Topic still represent a stimulus for future studies, their outcome aimed at providing evidence of the central position occupied by the adrenal cortex in many metabolic functions when its homeostasis is disrupted. An in-depth investigation of the mechanisms underlying these pathways will be invaluable in developing new therapeutic tools and strategies.
In the late 1980s, it became painfully evident to the pharmaceutical industry that the old paradigm of drug discovery, which involved highly segmented drug - sign and development activities, would not produce an acceptable success rate in the future. Therefore, in the early 1990s a paradigm shift occurred in which drug design and development activities became more highly integrated. This new str- egy required medicinal chemists to design drug candidates with structural f- tures that optimized pharmacological (e. g. , high affinity and specificity for the target receptor), pharmaceutical (e. g. , solubility and chemical stability), bioph- maceutical (e. g. , cell membrane permeability), and metabolic/pharmacokinetic (e. g. , metabolic stability, clearance, and protein binding) properties. Successful implementation of this strategy requires a multidisciplinary team effort, incl- ing scientists from drug design (e. g. , medicinal chemists, cell biologists, en- mologists, pharmacologists) and drug development (e. g. , analytical chemists, pharmaceutical scientists, physiologists, and molecular biologists representing the disciplines of pharmaceutics, biopharmaceutics, and pharmacokinetics/drug metabolism). With this new, highly integrated approach to drug design now widely utilized by the pharmaceutical industry, the editors of this book have provided the sci- tific community with case histories to illustrate the nature of the interdisciplinary interactions necessary to successfully implement this new approach to drug d- covery. In the first chapter, Ralph Hirschmann provides a historical perspective of why this paradigm shift in drug discovery has occurred.
This book provides a comprehensive compilation of the evidence available regarding the role of genetic differences in the etiology of human obesities and their health and metabolic implications. It also identifies the most promising research areas, methods, and strategies for use in future efforts to understand the genetic basis of obesities and their consequences on human health. Leading researchers in their respective fields present contributed chapters on such topics as etiology and the prevalence of obesities, nongenetic determinants of obesity and fat topography, and animal models and molecular biological technology used to delineate the genetic basis of human obesities. A major portion of the book is devoted to human genetic research and clinical observations encompassing adoption studies, twin studies, family studies, single gene effects, temporal trends and etiology heterogeneity, energy intake and food preference, energy expenditure, and susceptibility to metabolic derangements in the obese state. Future directions of research in the field are covered in the book as well.