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Comprehensive overview of different aspects of autophagy as it relates to neurodegenerative diseases. The pathogenesis of the main neurodegenerative disorders includes either the accumulation of altered or misfolded proteins or exposure to several toxics. Autophagy constitute one of the two principal cellular pathways implicate in the clearance of these material and can serve as a neuroprotective mechanism. Topics include: the role of autophagy in the brain, the role of autophagy in the principal neurodegenerative disorders, and the mechanism by which different molecules cause neurotoxicity and the role autophagy plays.

This book provides a series of comprehensive views on various important aspects of vertebrate photoreceptors. The vertebrate retina is a tissue that provides unique experimental advantages to neuroscientists. Photoreceptor neurons are abundant in this tissue and they are readily identifiable and easily isolated. These features make them an outstanding model for studying neuronal mechanisms of signal transduction, adaptation, synaptic transmission, development, differentiation, diseases and regeneration. Thanks to recent advances in genetic analysis, it also is possible to link biochemical and physiological investigations to understand the molecular mechanisms of vertebrate photoreceptors within a functioning retina in a living animal.Photoreceptors are the most deeply studied sensory receptor cells, but readers will find that many important questions remain. We still do not know how photoreceptors, visual pigments and their signaling pathways evolved, how they were generatedand how they are maintained. This book will make clear what is known and what is not known. The chapters are selected from fields of studies that have contributed to a broad understanding of the birth, development, structure, function and death of photoreceptor neurons. The underlying common word in all of the chapters that is used to describe these mechanisms is “molecule”. Only with this word can we understand how these highly specific neurons function and survive. It is challenging for even the foremost researchers to cover all aspects of the subject. Understanding photoreceptors from several different points of view that share a molecular perspective will provide readers with a useful interdisciplinary perspective.

This book is dedicated to Dr. Philip A. Schwartzkroin. The book has a novel format because it is not intended to be a set of reviews. Instead, it is an effort to explore important topics in the epilepsy research field. Because articles are written by leaders in the field who have years of experience and individuals with diverse expertise, articles are likely to have a long-lasting impact and be relevant for both epileptologists and neuroscientists. Authors address topics that are important, unresolved questions in the field of epilepsy research, drawing on available data from both the bench and the clinic to support their points. A given topic is addressed by one or more authors, each writing from his/her own unique perspective. For all of the individuals who have been trained or worked with Philip Schwartzkroin in the past and/or have appreciated his contributions to the epilepsy field, this volume is an excellent way to celebrate his achievements and look to the ways they have moved the field forward and continue to stimulate its growth.

Four chapters represent the intense current effort to understand the way in which the mitochondrion controls the activation of the final stages of cell death. Another four articles attack the problem from the other side. How do specific insults in particular human or mouse neuro-degenerative diseases translate into mechanisms that will not only allow us to better understand what is happening in these patients but also, with luck, allow for development of more efficient and specific drugs in the future? Firstly, the concept of a central common cell death pathway, originally derived from studies on the nematode, has been an outstanding productive paradigm in bringing together different strands of research. Secondly, truly striking links have been made between results obtained in the culture dish (or even cell-free systems) and the diseased human brain.

Volume 5 of the series'Advances in Research on Neurodegeneration'is concerned with themes which are currently the focus of intensive research, and in which advances in our understanding of the pathological mechanisms un­ derlying neurodegenerative diseases are expected in the near future. The first section contains five reviews devoted to the various neuroimaging technolo­ gies. The discussion is concerned with the question of whether neuroimaging techniques make it possible to follow the process of degeneration as it occurs, and which methods offer the required sensitivity and quantifiability for this purpose. However, the question needs to be examined of whether, given the physical and chemical limitations of these techniques, even under optimal conditions, anatomical resolution can be improved to the extent that neuro­ degenerative diseases can be diagnosed earlier than currently possible and a confident diagnosis made. The possibilities of using neuroimaging techniques to provide information regarding the effects of neuroprotective or neuroregen­ erative therapeutic strategies, and for correlating the results of neuropsycho­ logical research with imaging data are also discussed. The second section is concerned with the significance of endogenous or exogenous neurotoxins as triggers for neurodegenerative processes that may lead to Parkinsonism. Vulnerability factors, which include such factors as nerve ending sensitivity, the synergistic effects of drugs and the various mechanisms underlying different toxins are discussed.

Because of the dearth of experimental animal models of psychiatric disorders, the study of the effect of the disease state is only possible in tissue derived from patients vs. controls, especially in the target tissue of disease-related changes in the brain. The human postmortem brain offers the most appropriate experimental paradigm towards understanding the etiology of psychiatric disorders. The availability of post-mortem human samples from psychiatric patients and comparison groups in recent years has contributed prominently to the accumulating body of information leading to a better understanding of these disorders. This is the first book to summarize this research approach and the meaningful data which has recently been acquired.

Neurodegeneration is one of the most important subjects of the investigation now and in the coming 21st century. Alzheimer's disease is the leading cause of dementia in the elderly people and Parkinson's disease is one of the major neurologic disorders with the prevalence between 1 and 2/1 000 population in advanced countries. Many others are suffering from intractable neurodegener­ ative disorders such as amyotrophic lateral sclerosis, Huntington's disease, or spinocerebellar degeneration. No truly effective treatment is available for any of these neurodegenerative disorders except for Parkinson's disease; even in Parkinson's disease, still it is impossible to slow down the disease process with the currently available treatment. It is urgently needed to develop new effective technique to halt or slow down the disease process in each of those disorders. Recent advance in the molecular biological and molecular genetic technique has brought us great progress in the understanding of etiology and pathogenesis of these disorders, but still it is not known how neurons are going to die in these disorders. To explore the question, mutual cooperation and exchange of ideas between basic scientists and clinical peoples are of utmost importance.

Most of the world's experts on prions met for a workshop in Erice in August 1996. The aim of the workshop was to discuss the fundamentals of the science ofprions. It was for­ tunate that so many could be present given the pressure that they were under because of the data presented in March 1996, indicating that Bovine Spongiform Encephalopathy, BSE or Mad Cow Disease, had penetrated the species barrier and was beginning to cause a new dis­ ease in humans--the new variant ofCreutzfeldt-Jakob Disease, nvCJD. This important and urgent subject became an additional major topic at the workshop. This is a book containing most of the talks plus the abstracts of those unable to find time to write up their talks. Almost all papers were written in the spring and summer of 1997 and contain material added after the workshop; thus Bob Will's paper on the new variant of cm contains data up to July 1997 and four contributions arrived in October 1997. In addition to the talks given at our workshop, there was a special joint session with the Planetary Emergencies Workshop where many distinguished scientists, including three Nobel laureates, discussed major issues affecting our planet. Six talks were given by us to this other workshop, five about prions, BSE, and nvCJD, and one on the broader issue of new epi­ demics by Luc Montagnier. Although most of the talks concerned research issues, there were a few special talks.

In 1984, we organized a two-day symposium on retinal degenerations as part of the biennial meeting of the VI International Society for Eye Research, held in Alicante, Spain. The success of this first meeting led to the second held, two years later in Sendai, Japan, organized as a satellite of the VII ISER. We were fortunate that these meetings began at a time of vigorous research activity in the area of retinal degenerations, thanks to the financial support of the Retinitis Pigmentosa Foundation and the strong encouragement of its scientific director, Dr. Alan Laties. Significant advances were made so that every two years scientists were eager to meet to share their findings. The programs included presentations by both basic and clinical researchers with ample time for informal discussions in a relaxed atmos­ phere. Many investigators met for the first time at these symposia and a number of fruitful collaborations were established. This book contains the proceedings of the VI International Symposium on Retinal Degenerations held November 6-10, 1994, in Jerusalem. As with the other meetings, some new areas were covered. One session was devoted to apoptosis, an important process involved in cell death in inherited retinal degenerations. Another session was on invertebrate photoreceptors, where numerous mutations have now been identified that lead to altered function or degeneration of the retina. All participants were invited to submit chapters and most complied. We thank them for their contributions.

This expanded and updated edition reflects the enormous increase in our knowledge of the development of the nervous system and the use of neural stem cells in clinical applications. Integrating new information about the use of development of neural stem cells for clinical applications, Drs. Rao, Carpenter and Vemuri have added additional chapters on neural transplantation and development of neural stem cells using reprogramming technologies. A new chapter on cancer in nervous system delineates how the fundamental biology of neural stem cells informs our understanding of cancer and tumor formation in the nervous system. Special attention is paid to the derivation of neural cells from embryonic stem cells and induced pluripotent stem cells. Authoritative and up-to-date, Neural Development and Stem Cells, 3rd Edition provides neuroscientists with a handy guide to stem cells in the nervous system, tracing with great clarity the development of stem cells from differentiation to neurons, astrocytes, and oligodendrocytes.

Apoptosis is a fascinating concept for the basic scientist. This is not only because of the multifaceted variety of proposed and discovered mechanisms, but because apoptosis represents a fundamental pathway for cell renewal. The study of apoptosis has resulted in an array of discoveries on signal transduc­ tion and downstream effects that have facilitated and advanced many fields in biology, including research on cancer and other diseases. Thus, the apoptotic process can be viewed as the largest effort of the scientific community to understand how cells work and tissues assemble or remodel. The most direct consequence of this accumulated knowledge is a greater understanding of disease and pathological mechanisms. The end result of these efforts will be significant contributions to health and the adoption of new, never anticipated, therapeutic approaches. This book represents the summation of considerable effort from a significant group of contributors from all over the world as well as from its editors. In this fashion, many viewpoints have been collected and SUbjected to thorough academic discussion. The concepts contained in this medically important volume will stimulate and renew the ideas of scientists and indeed, will generate additional work to advance biological knowledge even further. The emphasis of this volume cements what has been established, adds what has not been explored fully, and creates a fertile ground for further hypotheses that will lead to a more complete understanding of the apoptotic process.

This volume sets a basis for effective translational research. Authored by experts in the field of translational stroke research, each chapter specifically addresses one or more components of preclinical stroke research. The emphasis is placed on target identification and drug development using state-of-the-art in vitro and in vivo assays, in combination with in vitro toxicology assays, AMDE and clinical design.

Proceedings of an international symposiu, held in Valencia, Spain, December 2-4, 1996

This book is the result of a convergence of scientific information regarding mechanisms that produce acute nerve cell death in the brain. Although seemingly disparate, stroke, brain and spinal cord trauma, coma from a low serum glucose concentration (hypoglycemia), and prolonged epileptic seizures have in common the inciting factor of excitotoxicity, the activation of a specific subtype of glutamate receptor by an elevated extracellular glutamate concentration that results in an excessive influx of calcium into nerve cells. The high calcium concentration in nerve cells activates several enzymes that are responsible for degradation of cytoplasmic proteins and cleavage of nuclear DNA, resulting in nerve cell death. The high calcium concentration also interferes with mitochondrial respiration, with the resultant production of free radicals that damage cellular membranes and nuclear DNA. Understanding the biochemical pathways that produce nerve cell death is the first step toward devising an effective neuroprotective strategy, the ultimate goal. Acute Neuronal Injury will be useful to neuroscientists and general cell biologists interested in cell death. The book will also be helpful to clinically oriented neuroscientists, including neurologists, neurosurgeons and psychiatrists. About the Editor: Dr. Denson Fujikawa is an Adjunct Professor of Neurology at the David Geffen School of Medicine at UCLA, a member of the Brain Research Institute at UCLA and a Staff Neurologist at the Department of Veterans Affairs Greater Los Angeles Healthcare System. His interest in mechanisms of nerve cell death in the brain began during a two-year epilepsy research fellowship with Dr. Claude Wasterlain, from 1981 to 1983. He is a Fellow of the American Academy of Neurology and is a member of the American Epilepsy Society, American Neurological Association, International Society for Cerebral Blood Flow and Metabolism, and the Society for Neuroscience.

Complex physiopathological relationships have been proven to exist between two of the body's most vital organs; the brain and the heart. In Cell Cycle Regulation and Differentiation in Cardiovascular and Neural Systems Antonio Giordano, Umberto Galderisi and a panel of the most respected authorities in their field offer an in-depth analysis of the differentiation process in two systems that have profound relationships with one another. The text looks at several aspects of the cardiovascular and nervous systems from a new point of view, describing the differences and similarities in their differentiation pathways with an emphasis on the role of cell cycle regulation and cell differentiation. Topics discussed include neurogenesis in the central nervous system, neural stem cells, and the basic-helix-loop-helix transcription factors in neural differentiation. Ground-breaking and authoritative, Cell Cycle Regulation and Differentiation in Cardiovascular and Neural Systems is a must have for all researchers in cardiovascular medicine and neuroscience and will prompt the scientific community to perceive cell cycle regulation and differentiation under a novel and more comprehensive light.

Interactions Between Neurons and Glia in Aging and Disease is a source of'reference reviews'and'concise overviews'of the functional cross-talk between neurons and glial cells, with a focus on microglia and inflammation in the aging brain and in neurological disorders. The scientific area covered by this book may be considered of key interest, and it is recognized, by the scientific community, as a major competitive area with critical implications for human health. This book is organized in three main sections that are expected to guide the readers from the basic functional cross-talk between neuron and glia to brain pathology. The specific proposed sections are: 1) Neuroimmunity and Neuroinflammation; 2) Signalling and inflammation in aging; 3) Neurodegeneration and inflammation in age related diseases.

In the last 50 years a wealth of information has allowed us to understand the contribution of various regulatory factors that alter mRNA and protein s- thesis to a variety of physiological and pathological conditions. However, such regulation is only one of many factors that contribute to the levels of a given p- tein. One major factor that has been relatively obscure until recently has been the contribution of protein degradation to the regulation of the steady state level of protein expression and protein function. This rapidly evolving field has made a significant mark on the scientific community, as highlighted by the Award of the Nobel Prize in Chemistry for 2004 to Aaron Ciechanover, Avram Hershko and Irwin Rose for their pioneering work on the ubiquitin-proteasome system (UPS) of protein degradation, which is the subject of this volume. In recent years e- dence has been accumulating that suggests a role for UPS function in both ph- iological and pathological settings. In particular, studies have implicated a central role for the UPS in cell cycle regulation, cancer and neurodegeneration. Two points are however worth bearing in mind: First, ubiquitin's function appears to extend far beyond the UPS and protein degradation; second, there are other important systems of intracellular protein degradation, most notably autophagic systems through the lysosomes, and these may also be involved in disease pat- physiology.

Brain Repair, addresses all relevant issues underlying the mechanisms of brain damage, brain plasticity and post-traumatic reorganisation after CNS lesions. This book is divided the three major sections that follow; cellular and molecular basis of brain repair, plasticity and reorganisation of neural networks, and experimental therapy strategies. Brain Repair is written by high profile, international experts who describe in detail the newest results from basic research and highlight new model systems, techniques and therapy approaches. Based on a careful analysis of the cellular and molecular reaction patterns of the CNS to lesions, the contributions cover possibilities for endogenous reorganisation and repair as well as exciting new therapies emerging from basic research, some of which have already been introduced into the clinics. Thus, this book is unique in bridging the gap between basic and clinical research. It will be a valuable tool for all students, researchers and clinicians interested in understanding the brain's capacity to cope with lesions and interested in learning about emerging new therapy concepts.

Since Bailey and Cushing (1926), all brain tumor classifications have been called histogenetic. The nosographic position that the tumor types progressively acquired in the classification systems derived from the resemblance of tumor cells to those of the cytogenesis, modified whenever new information became available from different biological research fields and especially from molecular genetics. Classically, on the basis of the rough correspondence between the mature/immature aspect of tumor cells and the benign/malignant biological behavior of the tumors, the histological labels contained a prognostic significance. The supposed origin of the tumors was thus a factor for prognosis. Later on, with the concept of anaplasia (Cox, 1933; Kernohan et al., 1949) new criteria were introduced for establishing the malignancy grades of tumors. Immunohistochemistry and later molecular genetics further refined the prognostic diagnoses, substantially increasing the opportunities to recognize the cell origin of tumors, beside revealing the pathogenetic mechanisms. Prognoses became more accurate, as required by the greater and more targeted possibilities of therapy.

The book is presented as a timeline of development with emphasis on human and vertebrate biology. Fully documented examples exhaustively illustrate general principles in viewing development of structure and function as an integrated unity. All chapters have been extensively revised by noted international specialists. The book incorporates the most recent studies and research, including advances in stem cells and genomics. New chapters on aging and glial biology have been added. Continuity with previous editions is maintained by retention of the historical perspective for which this title is known. The book stresses the universal aspects of the development of the nervous system in both vertebrates and invertebrates, especially at the cellular level, but also compares and contrasts different levels of neuronal organization, giving much attention to phylogenetic and individual variations in neuronal ontogeny. With its comprehensive and completely updated coverage, generous illustrations, and a table of contents that reads like a Who's Who in neuroscience, this new and expanded Fourth Edition is a must have book for the professional neurobiologist and others seeking definitive and authoritative information in this important field. Instructors, as well as graduate and advanced under-graduate students, will also appreciate its clearly presented information, historical references, and organization for classroom use.

In all organs of the body, proteases have critical roles to play both in normal development and functioning and in disease states. The brain is no exception to this, with proteases having emerging roles in synaptic plasticity, memory, neurodegenerative disorders such as Alzheimer's, Parkinson's and prion diseases, ischemia and traumatic brain injury, inflammatory and infectious diseases, and tumor progression. Proteases in the Brain brings together a wide range of topics under this central theme and highlights the large number of proteases involved in these normal and disease processes. Proteases in the Brain reviews the role and regulation of proteases in, Alzheimer's disease, brain ischemia and traumatic brain injury, human glioma, inflammatory and infectious diseases of the central nervous system, metabolism of the prion protein, modulating synaptic activity, multiple sclerosis, neuronal plasticity and memory consolidation, Parkinson's disease, processing, conversion and inactivation of neuropeptides. Proteases in the Brain is a timely and useful source of information both for those well-versed in the role of proteases in the brain, and for those who are beginning to realize the important role of this family of enzymes in brain function and dysfunction.

Multiple Sclerosis (MS) is an enigmatic immune mediated disease of the central nervous system that affects about 350,000 individuals in the US, and many more around the world. The mechanism of this disease is largely unknown and there is no cure for it. However, there are several well-characterized experimental animal models that help us understand and speculate about potential mechanisms of pathology in this disease. Many of the experimental therapies designed for this disease rely on testing the drugs in animal models before using it in clinical trials. This book combines for the first time the different experimental models for MS (including immune-mediated and viral) under one roof, and highlights aspects that are different or shared among these experimental models. It's aim is to improve our understanding of this devastating disease and help us think about potential additional therapies for it.

Lysosomes are membrane-surrounded organelles which are present in all animal cells. The importance of this organelle is underlined by an increasing number of human diseases, which are associated with an impaired function of the lysosomal compartment. This book summarizes the current state-of-the art knowledge about this unique organelle. It addresses the biogenesis of this compartment, the transport of lysosomal proteins, the role of the lysosomal membrane in lysosomal stability and transport, the function of lysosomal proteases and hydrolases, lysosomal storage disorders, and new concepts on how to treat these diseases. In addition to these classical topics, new insights into lysosomal functions are covered by chapters dealing with specialized lysosomes involved in bone resorption and plasma membrane repair, the lysosomal transciptome, and proteome and the emerging role of lysosomes in special forms of autophagy. This book will provide readers with a comprehensive overview into how this fascinating organelle works and how research in the field is developing.