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The remarkable family of proteins that can make us very ill—but can also be linked to long-term memory, immunity, and the origin of lifeOver the last decade, scientists have discovered the importance and widespread presence in the body of a remarkable family of proteins known as prion proteins. Research links various types of prion proteins to neurodegenerative diseases such as Parkinson's and Alzheimer's—and this has fueled the search for new drugs that could halt the progression of these terrible disorders. Other discoveries have revealed the essential roles prion proteins play in memory and immunity, and—in an extraordinary finding—the part they may have played in the beginnings of life on our planet. In this engaging and accessible book, Michel Brahic tells the story of these amazing and versatile proteins.Brahic, a leading researcher on diseases of the central nervous system, first describes the discovery of prions and their role in infection, beginning with early work on the animal disease scrapie and a mysterious human illness in New Guinea, apparently transmitted by cannibalism. Prions were eventually identified and named by Stanley Prusiner in the 1980s. (Brahic tells us Prusiner's alternate name for prion was “piaf.”) Prion proteins were then revealed as the cause of other illnesses, from “mad cow” disease and its human counterpart, Creutzfeldt-Jakob disease, to such noninfectious brain disorders as Parkinson's and Alzheimer's. While the prion proteins responsible for diseases are definitively “bad,” Brahic also explains that these abnormal prions are rare exceptions. Most of the time, prion proteins actually serve “good” and vital functions—and they may even have been present at the origin of life itself.

Human Caspases and Neuronal Apoptosis in Neurodegenerative Diseases elucidates elaborately the role of caspase enzymes implicated in the initiation of molecular events leading to neuronal apoptosis in the neurodegenerative disease. The book starts with introduction to neuropathology, neurogenetics, and epidemiology of neurodegenerative disease and illustrates the involvement of human caspases, neuronal apoptosis, apoptotic pathways, genetic polymorphisms, and several other factors and underlying mechanisms in the pathology of Alzheimer's disease, Parkinson's disease, and Huntington's disease. An important focus in all chapters is the intricate mechanisms and interplay that occur during or leading to neuron death in neurodegenerative diseases, along with disease pathobiology. - Provides in-depth knowledge about neurotoxic potential of transition metals, impaired mitochondrial dynamics in the brain neurons, mutant proteins Aß peptide, tau protein, a-synuclein, huntingtin protein and formation of Lewy bodies, reactive oxygen and nitrogen species, ubiquitin proteasome dysregulation, and many others in neurodegenerative diseases - Elucidates neurogenetics of gene APP, gene PSEN1, gene APOE, gene LRRK2, gene DJ1, and others in the pathology of neurodegenerative diseases - Explains caspases-mediated neuronal apoptosis in pathogenesis of Alzheimer's disease covering amyloidogenesis, caspase-activated DNase, rho-associated coiled coil–containing protein kinase 1, mammalian sterile 20-like kinase 1, role of synaptic loss, microglial TREM2 receptor, microglial LRP1 receptor, microglial advanced glycation end-product receptor, astrocytic glial a 7 subtypes of nAChR, NLRP3 inflammasome, P2X purinoreceptors, miRNAs, and many other factors - Demonstrates the role of caspases and apoptosis in Parkinson's disease covering truncation of a-synuclein, neuroinflammation, parkin protein, activation of microglial cells, extrinsic and intrinsic pathways of apoptosis,?tau314, and several other factors - Explains etiopathogenesis of Huntington's disease through covering clinically important topics as role of exon 1 HTT protein, ubiquitous nature of huntingtin, length of expanded polyglutamine tract, classically and alternately activated microglia, nuclear factor kappa B, kynurenine signaling pathway, tumor suppressor protein, PGC-1a gene, advanced glycation end-products, autophagy, and many other significant topics

Molecular Aspects of Neurodegeneration, Neuroprotection, and Regeneration in Neurological Disorders presents readers with comprehensive and cutting-edge information on the neurochemical mechanisms of various types of neurological disorders. The book covers information on signal transduction processes associated with neurochemistry of neurological disorders, including neurodegenerative, neurotraumatic, and neuropsychiatric disorders. The book also discusses risk factors, symptoms, pathogenesis, biomarkers, and the potential treatments of neurological disorders. The comprehensive information in this monograph may not only help in early detection of various neurological disorders, but will also promote the discovery of new drugs. - Provides a comprehensive overview of the molecular aspects of neurodegeneration, neuroprotection, and neuro-regeneration, along with therapeutic strategies for various types of neurological disorders - Provides cutting-edge research information on the signal transduction processes associated with the neurochemistry of neurological disorders - Discusses risk factors, symptoms, pathogenesis, biomarkers, and the potential for treatments of neurological disorders

Metabolic Drivers and Bioenergetic Components of Neurodegenerative Disease reviews how the different aspects of metabolic dysfunction and consequent pathology associated with neurodegenerative diseases, including Alzheimer's and Parkinson's, can be targeted by novel treatment approaches. Topics covered include Cellular Senescence in Aging and Age-Related Disorders: Implications for Neurodegenerative Diseases; Repurposing GLP1 agonists for Neurodegenerative Diseases; Ketotherapeutics for Neurodegenerative Diseases; Enhancing Mitophagy as a Therapeutic Approach for Neurodegenerative Diseases; Harnessing Neurogenesis in the Adult Brain – A Role in Type 2 Diabetes Mellitus and Alzheimer's disease; and much more. - Summarizes the impact of the metabolic hypothesis on underlying mechanisms of neurodegenerative diseases - Presents novel, potential treatment strategies based on the metabolic hypothesis for neurodegenerative diseases

This book provides a comprehensive overview of the role of neuroglia in neurodegenerative diseases. Neuroglia are the most abundant cells in the nervous system and consist of several distinct cell types, such as astrocytes, oligodendrocytes,and microglia. Accumulating evidence suggests that neuroglia participate in the neurodegenerative process, and as such are essential players in a variety of diseases, including Alzheimer's, Parkinson's, and Huntington's. Intended for researchers and students, the book presents recent advances concerning the biology of neuroglia as well as their interaction with neurons during disease progression. In addition, to highlight the function of neuroglia in different types of neurodegenerative disease, it also discusses their mechanisms and effects on protecting or damaging neurons.

This book focuses on neurodegenerative diseases which have become a major threat to human health. Neurodegenerative diseases are age related disorders and have become increasingly prevalent in the elderly population in recent years. Hence, there is an urgent need to study and develop new strategies and alternative methods for the treatment of neurodegenerative diseases. This book showcases the promises that nanobiotechnology brings in research, diagnosis, and treatment of neurodegenerative diseases. It is very beneficial for varied group of readers including nanotechnologists, biotechnologists, pharmacists, medical professionals, bioengineers, biochemists and researchers working in this field. Nanobiotechnology in Neurodegenerative Diseases include various chapters including neurodegeneration and neurodegenerative diseases, nanotechnology for the rescue of neurodegenerative diseases, promising potential of nanomaterials for diagnosis and therapy of neurodegenerativediseases, nanotechnology mediated nose-to-brain drug delivery, and formulation and characterization of intranasal nanoparticles of antiretroviral drugs.

This book provides comprehensive coverage of small fiber neuropathy (SFN), from diagnosis to therapy. It focuses on nerve degeneration and neuropathic pain, and their underlying pathology, physiology, psychophysics, genetics and imaging. In particular, this book describes and discusses the major advances in diagnostic techniques for assessing SFN. These include skin biopsy, evoked potentials, quantitative sensory testing and functional studies, as biomarkers of SFN.SFN is a common peripheral nerve disorder, but was often overlooked due to a lack of objective and specific diagnostic tests for the assessment of small nerve fibers. These fibers mediate thermal sensation, pain detection (nociception), and autonomic regulation. Major symptoms of SFN include neuropathic pain, impaired sensation and autonomic dysfunction. Neuropathic pain poses a diagnostic challenge to clinicians, an essential step for selecting appropriate treatment to relieve suffering.SFN frequently develops in systemic diseases such as diabetes mellitus, following chemotherapy, infections etc., or presents as a major feature of various genetic neuropathies (e.g. channelopathy and familial amyloidosis). In addition to describing these conditions which lead to SFN, this book also describes related syndromes of neurodegeneration and pain, including fibromyalgia, visceral pain and hypersensitivity.This definitive book covers both clinical aspects and research progress, which provides in-depth and up-to-date information on SFN. It would be immensely useful for clinicians, neurologists, neuroscientists, diabetologists, and pain specialists. Dr. Sung-Tsang Hsieh is a professor at Department of Neurology and Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taiwan. He is also the associate dean of College of Medicine, National Taiwan University, Taiwan. Dr. Praveen Anand is a professor at Department of Clinical Neurology and head of Centre for Clinical Translation, Hammersmith Hospital, UK. Dr. Christopher Gibbons is an associate professor of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, USA. Dr. Claudia Sommer is a professor of Neurology at the Department of Neurology, Würzburg University Hospital, Germany.

Late aging associated changes in alcohol sensitivity, neurobehavioral function, and neuroinflammation, Volume 148, the latest release in the International Review of Neurobiology series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics. Each chapter is written by an international board of authors. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in the International Review of Neurobiology series - Includes the latest information on late aging-associated changes in alcohol sensitivity, inflammation and cognitive decline

Mitochondrial Neuropathies, Volume 146, brings together experts in a range of diseases that damage the nervous system to present the role of mitochondrial dysfunction in their particular field, with this new release focusing on Mitochondrial dysfunction in Alzheimer's Disease, HIV and the mitochondrial: immune interface in the CNS, The Impact of mitochondrial damage in HIV-induced peripheral neuropathy, Mitochondrial dysfunction and the pathogenesis of chemotherapy-induced peripheral neuropathy, Disorders of mitochondrial biogenesis in peripheral neuropathy, Mitochondrial dysfunction and the pathogenesis of diabetic neuropathy, Manipulating mitochondria to treat peripheral neuropathy, and DCA therapy - the yin and yang of mitochondrial activation. - Contains contributions from a diverse group of experts - Presents a timely resource that brings together different fields to highlight a common pathogenic mechanism - Focuses on the role of mitochondria in diverse neuropathies

This book gives an overview of the current knowledge on the most common neurodegenerative diseases, including Alzheimer's disease, frontotemporal lobar degeneration, Lewy body dementia,Parkinson's disease, amyotrophic lateral sclerosis, and additional less common neurodegenerative diseases. Both clinical and basic aspects of each disease are treated, including novel diagnostic criteria, old and new treatments, basic discoveries (genetics, epigenetics and molecular biology), and translation of basic research into biomarkers for early diagnosis, particularly to identify peripheral biomarkers. In addition, emerging data indicate that neurodegeneration seems to also be present in classically non-degenerative disorders. Therefore, a chapter about overlapping mechanisms between dementias and psychiatric disorders is included, as well as a description of the role of neurodegeneration in multiple sclerosis.Neurodegenerative Diseases is aimed at clinicians, particularly those workingin academic hospitals. This multidisciplinary book will also be of interest to basic researchers in medical fields.

The Molecular and Clinical Pathology of Neurodegenerative Disease brings together in one volume our current understanding of the molecular basis of neurodegeneration in humans, targeted at neuroscientists and graduate students in neuroscience, and the biomedical and biological sciences. Bringing together up-to-date molecular biology data with clinical evidence, this book sheds a light on common molecular mechanisms that underlie many different neurodegenerative diseases and addresses the molecular pathologies in each. The combined research and clinical background of the authors provides a unique perspective in relating clinical experiences with the molecular understanding needed to examine these diseases and is a must-read for anyone who wants to learn more about neurodegeneration. - Provides an up-to-date summary of neurodegeneration at a molecular, cellular, and tissue level for the most common human disorders - Describes the clinical background and underlying molecular processes for Alzheimer's disease, Parkinson's, Prion, Motor Neuron, Huntington's, and Multiple Sclerosis - Highlights the state-of-the-art treatment options for each disorder - Details examples of relevant cutting edge experimental systems, including genome editing and human pluripotent stem cell-derived neuronal models

It has become evident over the last years that abnormalities in RNA processing play a fundamental part in the pathogenesis of neurodegenerative diseases. Cellular viability depends on proper regulation of RNA metabolism and subsequent protein synthesis, which requires the interplay of many processes including transcription, pre--‐mRNA splicing, mRNA editing as well as mRNA stability, transport and translation. Dysfunction in any of these processes, often caused by mutations in the coding and non--‐ coding RNAs, can be very destructive to the cellular environment and consequently impair neural viability. The result of this RNA toxicity can lead to a toxic gain of function or a loss of function, depending on the nature of the mutation. For example, in repeat expansion disorders, such as the newly discovered hexanucleotide repeat expansion in theC9orf72 gene found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a toxic gain of function leads to the formation of RNA foci and the sequestration of RNA binding proteins (RBPs). This in return leads to a loss of function of those RBPs, which is hypothesized to play a significant part in the disease progression of ALS and FTD. Other toxicities arising from repeat expansions are the formation of RNA foci, bi--‐directional transcription and production of repeat associated non--‐ATG (RAN) translation products.This book will touch upon most of these disease mechanisms triggered by aberrant RNA metabolism and will therefore provide a broad perspective of the role of RNA processing and its dysfunction in a variety of neurodegenerative disorders, including ALS, FTD, Alzheimer's disease, Huntington's disease, spinal muscular atrophy, myotonic dystrophy and ataxias. The proposed authors are leading scientists in the field and are expected to not only discuss their own work, but to be inclusive of historic as well as late breaking discoveries. The compiled chapters willtherefore provide a unique collection of novel studies and hypotheses aimed to describe the consequences of altered RNA processing events and its newest molecular players and pathways.

Provides a timely overview of critical advances in molecular and cellular neurobiology, covers key methodologies driving progress, and highlights key future directions for research on neuronal injury and neurodegeneration relevant to neuronal brain pathologies. The editors bring together contributions from internationally recognized workers in the field to provide an up to date account of how and why molecular and cellular neurobiology is such an important area for clinical neuroscience. Understanding the molecular aspects of a number of neurodegenerative conditions such as Parkinson's or Alzheimer's disease for the purpose of improving patient management remains a major challenge of neurobiology be it from the basic or clinical perspective. A strategic evaluation of research contributions and the power of modern methods will help advance knowledge over the next years.

Environmental Factors in Neurodegenerative Diseases, Volume One addresses contemporary advances in neurotoxicology, with thematic volumes providing authoritative review articles on key issues in the field. Updates in this new volume include chapters on Air pollution and neurodegenerative diseases, Mercury and Parkinson's disease, Pesticides and PD: current evidence, Aluminum and neurodegeneration, Microglia and neurodegeneration, Dietary factors, Mitochondria in neurodegeneration, and Manganese and neurodegeneration. Edited by leading experts, volumes are designed as in-depth overviews of the latest topic developments that analyze the effect of varied chemical agents on the nervous system. It is an essential resource for researchers and graduate students alike. - Includes, in one single publication, a selection of comprehensive reviews devoted to neurotoxicology - Edited by high-profile, leading academics in the field, ensuring a quality publication for subscribers - Aims to widen the scope for participation by international contributors, researchers and editorial board members outside North America - Serves a broad audience of university faculty, researchers and students, as well as the industry, drug development companies and the government

This second edition brings together up-to-date contributions from leaders in the field internationally on the various ways in which mitochondrial dysfunction contributes to the pathogenesis of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and multiple sclerosis. The reader is guided through the basic functions of mitochondria and the mechanisms that lead to their dysfunction, and on to the consequences of this dysfunction for neuronal function before finishing with the modelling of these disorders and discussion of new potential therapeutic targets. Additional chapters have been added to the book to reflect advances in the field and there are many new contributors and topics, including how mitochondria are degraded and the interaction of the mitochondria with pathologically relevant proteins. Mitochondrial Dysfunction in Neurodegenerative Disorders provides an accessible, authoritative guide to this important area for neurologists; research and clinical neuroscientists; neuropathologists; and residents with an interest in clinical research.

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 sheds new light on neurodegenerative disorders as systemic diseases. Classically, neuronal cell death was a hallmark of such disorders. However, it has become evident that neural dysfunction is more important in the pathophysiology of neurodegenerative disorders. More recently, the prionoid-spreading hypothesis of disease-causing molecules has attracted a great deal of attention. Therapeutic strategies thus must be reconsidered in the light that neurodegenerative disorders are indeed systemic diseases. The first part of this book introduces the concept of neurodegeneration in biology and pathophysiology. The second part focuses on clinical evaluation and biomarkers from the perspective of this new concept, while the third summarizes the risk factors of neurodegeneration. The fourth part of this work indicates future directions of treatment, and the final part discusses health promotion for prevention and quality of life. This book will be of interest to both researchers and medical personnel, and provides a fresh approach to neurodegenerative diseases, paving the way to new research and improved quality of health care for patients.

The 1st World Congress on Geriatrics and Neurodegenerative Disease Research (GeNeDis 2014), will focus on recent advances in geriatrics and neurodegeneration, ranging from basic science to clinical and pharmaceutical developments and will provide an international forum for the latest scientific discoveries, medical practices and care initiatives. Advanced information technologies will be discussed concerning the various research, implementation and policy, as well as European and global issues in the funding of long-term care and medico-social policies regarding elderly people. GeNeDis 2014 takes place in Corfu Greece, 10-13 April 2014. This volume focuses on the sessions from the conference on computational biology and bioinformatics.

The 1st World Congress on Geriatrics and Neurodegenerative Disease Research (GeNeDis 2014), will focus on recent advances in geriatrics and neurodegeneration, ranging from basic science to clinical and pharmaceutical developments and will provide an international forum for the latest scientific discoveries, medical practices and care initiatives. Advances information technologies will be discussed along with their implications for various research, implementation and policy concerns. In addition, the conference will address European and global issues in the funding of long-term care and medico-social policies regarding elderly people. GeNeDis 2014 takes place in Corfu, Greece, 10-13 April 2014. This volume focuses on the sessions that address neurodegenerative diseases.

Omic Studies of Neurodegenerative Disease: Part A is part of a well-established international series on neuroscience that examines major areas of basic and clinical research, along with emerging and promising subfields. The book informs the reader on the current state of the studies used to evaluate the mechanisms, causes, and treatment of neurodegeneration through a combination of literature reviews and examples of current research. - Provides the expertise of leading contributors in the field - Demonstrates how findings in the fields of genomics, proteomics, and metabolomic studies can combined for further insights - Informs the reader on the current state of the studies used to study the mechanisms, causes, and treatment of neurodegeneration through a combination of literature reviews and examples of current research

Unless new discoveries are made in the prevention or treatment of stroke, Alzheimer's Disease and depression, the number of patients with these diseases is sure to increase dramatically by the year 2050. Thus, developing strategies to retard or delay the onset of stroke, AD and depression these neurological disorders is of critical important. The present monograph will provide current and comprehensive information on the relationship between neuroinflammation and oxidative stress in age-related neurological disorders at the molecular level. The information described in this monograph on lifestyle (diet and exercise), genes and age is intended to facilitate and promote new discoveries for the treatment of age-related neurological disorders.

This book gives an overview of the current knowledge on the most common neurodegenerative diseases, including Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and additional neurodegenerative diseases. Different aspects of each disease are reviewed, including clinical issues, treatments, basic discoveries (genetics and molecular biology), and translation of basic research into biomarkers for early diagnosis. In addition, emerging data indicate that neurodegeneration seems to also be present in classically non-degenerative disorders. Therefore, a chapter about overlapping mechanisms between dementias and psychiatric disorders is included, as well as a description of the role of neurodegeneration in multiple sclerosis.Neurodegenerative Diseases is aimed at clinicians, particularly those working in academic hospitals. This multidisciplinary book will also be of interest to basic researchers in medical fields.

This book will compile a collection of chapters dedicated to varied aspects of PPPM in neuropsychiatric and neurodegenerative diseases. Among the topics to be covered are:Recent advances in ALS research News about Clinical aspects and advanced therapy approaches in personalized treatment of ALS Schizophrenia: New treatments and clinical aspects Predictive, Preventive and Personalised Medicine in aging macular degeneration Advances in Multiple Sclerosis Pharmacogenetics, Tailoring Treatment Efficacy, Safety and Regimen Selection Multiple sclerosis related biomarkers: perspectives for clinical application Preventive clinical trials in brain aging: new trends & the need of guidelines MCI_ clinical guidelines in early diagnosis of dementia Alzheimer's disease: diagnostics, prognostics and the road to prevention Biomarkers for early diagnosis of Parkinson's and Alzheimer's diseases Synucleinopathies, tauopathies, TDP-43 proteinopathies and amyloidosis PSP, MSA and other parkinsonisms

A fundamental change is occurring in the understanding of the major neurodegenerative disorders. Protein aggregation is a common emerging theme in diseases as diverse as Alzheimer's, Creutzfeld-Jakob, Parkinson's, and amyotrophic lateral sclerosis. If valid, then a small number of diagnostic and rational therapeutic strategies will emerge over the next few years, based on the common theme of modulation of the production, turnover and deposition of these aggregating proteins. The book provides insights into the cellular and animal models of these diseases, and how the molecular basis of neurodegeneration has become the preferred target of therapy.

The misfolding and aggregation of specific proteins is an early and obligatory event in many of the age-related neurodegenerative diseases of humans. The initial cause of this pathogenic cascade and the means whereby disease spreads through the nervous system, remain uncertain. A recent surge of research, first instigated by pathologic similarities between prion disease and Alzheimer's disease, increasingly implicates the conversion of disease-specific proteins into an aggregate-prone b-sheet-rich state as the prime mover of the neurodegenerative process. This prion-like corruptive protein templating or seeding now characterizes such clinically and etiologically diverse neurological disorders as Alzheimer´s disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration. Understanding the misfolding, aggregation, trafficking and pathogenicity of the affected proteins could therefore reveal universal pathomechanistic principles for some of the most devastating and intractable human brain disorders. It is time to accept that the prion concept is no longer confined to prionoses but is a promising concept for the understanding and treatment of a remarkable variety of diseases that afflict primarily our aging society. ​

The editor of this volume, having research interests in the field of ROS production and the damage to cellular systems, has identified a number of enzymes showing ·OH scavenging activities details of which are anticipated to be published in the near future as confirmatory experiments are awaited. It is hoped that the information presented in this book on NDs will stimulate both expert and novice researchers in the field with excellent overviews of the current status of research and pointers to future research goals. Clinicians, nurses as well as families and caregivers should also benefit from the material presented in handling and treating their specialised cases. Also the insights gained should be valuable for further understanding of the diseases at molecular levels and should lead to development of new biomarkers, novel diagnostic tools and more effective therapeutic drugs to treat the clinical problems raised by these devastating diseases.

As age related diseases increase in prevalence and impact more significantly on medical resources it is imperative to understand these diseases and the mechanisms behind their progression. New research has stimulated a growing interest in mitochondrial involvement in neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and multiple sclerosis and the mechanisms which lead from mitochondrial dysfunction to neurodegeneration. Mitochondrial Dysfunction in Neurodegenerative Disorders brings together contributions from leaders in the field internationally on the various ways in which mitochondrial dysfunction contributes to the pathogenesis of these diseases, guiding the reader through the basic functions of mitochondria and the mechanisms that lead to their dysfunction, to the consequences of this dysfunction on neuronal function before finishing with the modelling of these disorders and discussion of new potential therapeutic targets. Mitochondrial Dysfunction in Neurodegenerative Disorders provides an accessible, authoritative guide to this important area for neurologists; research and clinical neuroscientists; neuropathologists; and residents with an interest in clinical research.

Twenty-five years ago, Earl R. Stadtman, PhD discovered that specific enzymes regulating metabolism can be inactivated by oxidation [1]. He later showed that age-related oxidative modification contributes, at least in part, to age-related loss of function of the enzymes [2, 3]. Dr. Stadtman broke the ground for a new field of study to discover how oxidative stress contributes in significant ways to age-related cellular dysfunction and protein accumulation and that oxidation in the aging brain influences Alzheimer's disease, ischemia-reperfusion injury, amyotrophic lateral sclerosis, and lifespan [4–6]. Today, his research and mentorship have positively influenced the work of hundreds of scientists in this field. We dedicate this book to Dr. Earl R. Stadtman (1912–2008), in celebration of his passion for science and his superior collaborative and mentorship skills. This book is comprised of three sections. The first describes the valuable roles reactive oxygen species (ROS) and reactive nitrogen species (RNS) play in cellular biology. The second section provides an overview of redox imbalance injury with effects on mitochondria, signaling, endoplasmic reticular function, and on aging in general. The third section takes these mechanisms to neurodegenerative disorders and provides a state-of-the-art look at the roles redox imbalances play in age-related susceptibility to disease and in the disease processes. In the first section we attempt to answer a question posed by Dr. Stadtman, ‘‘Why have cells selected reactive oxygen species to regulate cell signaling events''[7].

In the past decade, our understanding of the biochemistry, molecular biology, and neuropathology of the glutamate transporters and receptors has exploded. It is becoming increasingly evident that molecular mechanisms, which govern the transfer of the death signal from the neural cell surface to the nucleus, depend on lipid mediators and on cross talk among excitotoxicity, oxidative stress, and neuroinflammation, and that interactions among these three processes play a major role in neuronal cell death during acute neural trauma and neurodegenerative disease. These processes may be primary initiating points in neurodegeneration or they may be the end result of the neurodegenerative process itself. Neurochemical Aspects of Excitotoxicity provides extensive insight into glutamate transporters and receptors, including their role in the brain with other neurochemical parameters in excitotoxicity, and possible treatments. This book will be of interest scientists already working in the field of excitotoxicity who are interested in gaining a broader understanding of this complicated subject area, as well as graduate students and neurologists who are curious about a common cause of neuronal injury and neurological disorders.

Neurobiology of Disease is aimed at any basic scientist or clinician scientist teaching a course or conducting research on the basic science underlying the major neurological diseases. It provides an excellent overview of cutting-edge research on the fundamental disorders of the nervous system, including physiological and molecular aspects of dysfunction. The major categories of neurological disease are covered, and the chapters provide specific information about particular diseases exemplifying each of these categories. Sufficient clinical information is included to put into perspective the basic mechanisms discussed. The book assembles a world-class team of section editors and chapters written by acknowledged experts in their respective fields. - Provides cutting edge information about fundamental mechanisms underlying neurological diseases - Amply supplied with tables, illustrations and references - Includes supporting clinical information putting the mechanisms of disease into perspective

Neuroinflammation has been implicated recently in the pathogenesis of many neurodegenerative diseases. The cross-talk between neurons and non-neuronal cells seems to be a critical step in the progression of neurodegeneration and molecules that have a beneficial role may turn into harmful players. Thus, matrix metalloproteinases (MMPs), which are involved in axonal growth and regeneration as well as synaptic plasticity, may also have detrimental effects. Recent evidence has linked MMPs to conditions like ischemia, multiple sclerosis, Alzheimer's disease and suggested that, together with their role in the degradation of extracellular macromolecules, MMPs could work as important signalling molecules from injured neurons to the microglia. Thus, MMP-3 has been shown to induce the release of pro-inflammatory cytokines from microglia via activation of ERK and NF-kB-dependent pathways. Increasing evidence highlights the importance of a balanced cross-talk between neurons and non-neuronal cells and indicates that the presence of reactive astrocytes, the activation of microglia and the release of inflammatory mediators may contribute to the progression of many central nervous system disorders, independently of the nature of the primary pathogenic event. However, many aspects still remain controversial and much more effort is needed to understand the role of neuroinflammatory mediators and processes in these conditions. This volume brings together renowned, international scientists to discuss current knowledge and views on the mechanisms of neuroinflammation, on its role in the context of different neurodegenerative diseases (i.e. Alzheimer's, prion disease, HIV-associated dementia, multiple sclerosis, pain) and on the potential approaches for future therapeutic strategies.

Recognition that aging is not the accumulation of disease, but rather comprises fundamental biological processes that are amenable to experimental study, is the basis for the recent growth of experimental biogerontology. As increasingly sophisticated studies provide greater understanding of what occurs in the aging brain and how these changes occur

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.

David R. Brown Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK In 1982 Stanley Prusiner and colleagues puri?ed an abnormal protein from the brains of mice experimentally infected with a rare sheep dis- 1 ease called scrapie. This protein was called the prion protein. Earlier work had suggested that this diseases and others, loosely collected - gether as transmissible spongiform encephalopathies (TSEs), were not transmitted by conventional infectious agents. Prusiner suggested that 2 this new protein was the infectious agent in these diseases. Such a contentious suggestion lead to ferocious debate. Many researchers still maintained that there was no such thing as an infectious protein. - spite this, by 1990 most people accepted that the cause of the TSEs was the abnormal isoform of the prion protein his research group had id- ti?ed. The most convincing evidence for this had come from the work of Charles Weissmann, whose prion protein knockout mice could not be infected because they lacked expression of the protein that was now 3,4 forever linked to these disease. Since then it has become more widely accepted for these diseases to be termed prion diseases. In 1997 when 5 Stanley Prusiner won the Nobel Prize for his work on prion diseases. Even then, there was still an element of resistance in the scienti?c c- munity. It was considered that, in order the transmissible agent to truly be a protein only, the protein would have to be generated from a rec- binant source.

Given the very limited capacity of regeneration in the brain, protecting neurons that are on the brink of death is a major challenge for basic and clinical neuroscience, with implications for a broad spectrum of acute and chronic neurological and psychiatric diseases. This book brings together leading experts from neurobiology, neurophysiology, neuropharmacology, neuroimmunology and clinical neuroscience to highlight the most recent milestones in this rapidly evolving field. The book will serve as a reference for both basic neuroscientists and clinicians interested in an authoritative update on the molecular and cellular biology of neuroprotection and its promises for new therapeutic strategies.

This volume provides an up-to-date survey of current thinking concerning the actions of chemical factors in the regulation of neuronal behaviour under normal and pathological conditions. The book is divided into four sections, dealing with chemical factors involved with the formation of axon pathways, factors involved with neuronal survival and specialization during normal development, factors involved in normal maintenance and repair of adult neurons and, finally, factors that have been implicated as mediators of degenerative changes in neurological and neuropsychiatric disorders.