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In neurosciences one may say, '"All roads lead to Rome. " It seems as though wherever one starts, the course of investigation leads to the same major ques tions about nervous system function and dysfunction. In thinking about what to write in this preface, it occurred to me that it might be best to deal with that with which I am most familiar and to trace to some extent my own '"road to Rome. '' As I look over my work of the last 37 years, it becomes clear to me that it can be epitomized as a search for patterns. What usually began as a single minded devotion to in-depth analysis of one or a small number of variables always has led to questions of how the results might relate to the whole living unit, whether it is cell, tissue, or organism. For a number of years after my discovery in the vertebrate central nervous system of -y-aminobutyric acid (GABA) and the enzyme which forms it, L glutamate decarboxylase (GAD), and the identification of GABA as a major inhibitory neurotransmitter by others, I felt that my laboratory, largely bio chemical, was wandering in the wilderness of the complexities of the vertebrate CNS without definitively coming to terms with problems related to GABAergic transmitter functions and the roles of GABA neurons in information processing.
It has been recognized for more than a thousand years that the function of the brain, like the function of the other organs of the body, is determined by its physical, chemical, and biological properties. Evidence that even its highest functions could be explained by these properties was gathered only in recent years, however; these findings, which clearly have to be confirmed by a great deal of further experimental evidence, indicate that most, if not all, of the functions of the brain are based on its bio chemical and biophysical mechanisms. This at first hearing may sound rather simple, but the ability to understand learning, emotion, perhaps even creativity, on biological terms may well be the most important scientific discovery of all time. Few pieces of knowledge can influence our future health and well-being to the degree that understanding of mental mechanisms will. It has been clearly shown in many ways in the previous volumes of this Handbook that from the biochemical or neurochemical point of view the brain is one of the most active organs. The brain seems stable and in some respects permanent; this is evidence not of inactivity but of carefully controlled homeostasis, of dynamic rather than static equilibrium, with most components undergoing metabolic alterations.
This volume is concerned with metabolic reactions occurring in the nervous system. Some time ago, it was thought that since most of the intermediary metabolism that can be observed in the brain is not specific to this organ, there is little justification in studying neural metabolism as such. Later it was realized that for an understanding of neural functions, the understanding of metabolism in the brain and its alterations is essential. All aspects of the metabolism of a substrate in brain, or all metabolic reactions of the nervous system, could not be included in this volume; some will be dealt with in other volumes (such as the ones covering metabolic turn over, alterations of metabolism, or pathology). Review of the aspects covered here clearly shows that the study of metabolic reactions in the nervous system is a very active field, producing important results. As in so many areas of research, as we learn more, new aspects become known, new questions emerge, and we see that in solving some problems we open areas with many additional problems to solve. But the accomplishments to date are impressive and indicate further important advances in the future. Brain metabolism is more active, more plastic, and more comprehensive than previously estimated. It is an essential part of brain function, and with its alteration, brain function will be altered. This shows the importance of more knowledge in this area. It is hoped that this volume will be of assistance in such further studies.
Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
Nuclear receptors are a family of transcription factors consisting of 49 members identified in the human genome. Nuclear receptors regulate transcription by binding to response elements in the regulatory regions of target genes and thereby affect expression of genes involved in differentiation, growth, lipid homeostasis, inflammation and immunity. Over the past two decades significant advances have been made in the understanding of the regulation of gene expression by nuclear receptors. The knowledge on nuclear receptors has delivered novel therapies for lipid control and hormone replacement, and for management of cancer and diabetes. Therefore, nuclear receptors are attractive molecular targets for design of therapy for diabetes, obesity, atherosclerosis, cancer, inflammation and neurodegeneration. The focus of this volume is centered on the mechanistic involvement of nuclear receptors in cardiological, metabolic and neurological disorders, on possible explanation of pathways involved in pathogenesis, on susceptibility to and prevention of metabolic and neurological disorders and on the aspects of drug finding including chemistry and rational drug design. This volume reviews recent progress on nuclear receptors critically and will intrigue those pursuing interest in physiology, pathology and medicine.
Offering a comprehensive review of the neuropathology of SARS-CoV-2, Neurological Care and the COVID-19 Pandemic provides up-to-date coverage of the wide array of the pathogen's neurological symptoms and complications. Drs. Ahmad Riad Ramadan and Gamaledin Osman discuss the neuropathology of SARS-CoV-2, its neurological manifestations, and the impact the pandemic has had on the care of patients with pre-existing neurological conditions. The authors also offer an overview of emerging treatments and vaccines, as well as ways healthcare systems have reorganized in order to respond to the pandemic. - Offers a thorough discussion of the impact the virus has had on the care of patients with neurological ailments, accompanied by recommendations on how to care for these patients. - Covers the impact of COVID-19 on patients with cerebrovascular diseases, seizures, demyelinating diseases, neuromuscular disorders, movement disorders, headache disorders, cognitive disorders, and neuro-oncological disorders. - Includes a detailed case study of how one healthcare system hit hard by COVID-19 successfully transformed itself to respond to the challenges imposed by the pandemic. - Consolidates today's available information on this timely topic into a single, convenient resource.
ill recent years, it has become clearly recognized that many behavioural disturb ances and psychiatric illnesses are intimately associated with alterations in neuroendocrine function. This volume is designed to provide a thorough, up-to date review of our current knowledge of the neuroendocrine correlates of altered behaviour in man and experimental animals. Particular emphasis has been focused on the mechanisms which may underlie the coupling of mental functions with endocrine changes and the possible common links in the central regulation of both endocrine and psychic activities. One of the main objectives of this book is to consider both the experimental and clinical approaches in studying the interrelationship between neuroendocrine regulation and altered behaviour, and to assess its importance in the pathogenesis, diagnosis and treatment of mental disorders. The book has been organized into four major sections which focus on: (i) the role of pituitary hormones in the regulation of CNS function; (ii) the relationship between brain endorphin systems, psychotropic drugs and neuroendocrine regulation; (iii) the importance of neuroendocrine regulation in the pathogenesis of mental disorders; and (iv) biological markers of altered mental function. Each chapter is organized for ease of comprehension as well as for rapid retrieval of progress and essential information concerning the neuroendocrine basis of altered behaviour and psychiatric illnesses. The contributing authors were selected because of their widely recognized expertise in the field.