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Vitamins and Hormones series, highlights new advances in the field, with this new volume presenting interesting chapters. Each chapter is written by an international board of authors. - Provides the latest information on blood-brain barrier research - Offers outstanding and original reviews on a range ofblood-brain barrier research topics - Serves as an indispensable reference for researchers and students alike

This book deals with neurotrophins (NGF, BDNF, NT3, NT4), which can decrease cell death, induce differentiation, as well as sustain the structure and function of neurons. This makes neurotrophins potential therapeutic agents for the treatment of neurodegenerative disorders. However, these proteins have so far been ineffective in clinical trials mostly because they cannot pass the blood-brain barrier owing to their high-molecular weights. Consequently, small molecules that mimic neurotrophins and stimulate the synthesis of endogenous neurotrophins or enhance their neurotrophic actions are expected to be promising alternatives. Small-molecule natural products, which have been used in dietary functional foods or in traditional medicine over the course of human history, have potential to be developed as new therapeutic agents against neurodegenerative conditions such as Alzheimer's disease. In this book, the authors introduce a variety of natural products possessing neurotrophic properties such as neurogenesis, neurite outgrowth promotion (neuritogenesis), and neuroprotection and focus on the chemistry and biology of several neurotrophic natural products.

This book provides a comprehensive overview of the role of exosomes in brain diseases, including stroke, multiple sclerosis, Parkinson's disease, Alzheimer's disease, epilepsy, and depression. It covers the basics of exosome biogenesis, composition, and synthesis, as well as the therapeutic potential of exosomes in brain disorders. The correlation between exosomes and neuroinflammation, the challenges of using exosomes as a novel carrier, and engineered exosomes to deliver therapeutic protein are covered well in this book. Use of radiolabelled exosomes as a diagnostic tool and the toxicity studies of exosomes with potential overcome approaches. It is an essential resource for researchers, clinicians, and healthcare professionals working in the field of exosome research, especially on its applications in brain disorders.

Glycolysis: Tissue-Specific Metabolic Regulation in Physio-Pathological Conditions provides an integrated overview of glycolysis, spanning basic biochemistry, patho-physiology and therapeutic applications. The book also instructs in methods available to study the involvement of the glycolytic events in healthy biology and disease pathology. It begins with an overview of fundamental glycobiology followed by chapters dedicated to glycolysis physiology in organs and systems, pathologic conditions related to glycolytic alterations, glycolysis as a therapeutic target and in drug discovery efforts, and methodological approaches to advance new glycolysis research. Disease areas considered range from cancer to heart failure, diabetes, inborn glycolytic pathway defects, hematologic malignancies, osteoporosis, neurodegenerative diseases and viral Infections. Omics and computational modeling, interactive study methods, and glycolysis flux measurement are described in detail, with step-by-step descriptions of experimental protocols, set-up and analysis. - Features chapter contributions from international leaders in the field - Spans fundamental aspects of glycolysis, patho-physiology and drug discovery - Includes step-by-step instruction in a range of research protocols, ranging from Omics to interactive analysis and measuring glycolysis flux

Metalloenzymes: From Bench to Bedside offers a thorough overview of metalloenzymes, spanning biochemical and structural features, pharmacology, and biotechnological applications. After a brief overview, international experts in the field discuss a wide range of magnesium, calcium, zinc, manganese, nickel, iron, copper, cadmium, molybdenum, and tungsten enzymes, along with catalytic roles within their active sites. With a uniform approach throughout, each chapter includes the structure and function of the enzyme, physiologic and pathologic roles, inhibitors and activators of the enzyme (and their design), and clinical agents or compounds applied in medicine and drug discovery. This book enables scientists across academia and industry to adopt ongoing metalloenzyme research, and continuous discovery of novel metalloenzymes, in new life science studies and clinical applications. - Examines a range of metalloenzymes, from biochemistry to pharmacology and drug design - Each chapter examines enzyme structure and function, physiologic and pathologic roles, inhibitors and activators, and clinical application - Features chapter contributions from international experts in the field

This updated and expanded volume gives new insights on ferroptosis – an iron-dependent form of non-apoptotic cell death. The collection of chapters discusses the two major pathways through which ferroptosis can occur: the extrinsic or transporter-dependent pathway and the intrinsic or enzyme-regulated pathway.Readers will gain an understanding of the multiple levels, on which this special cell death is regulated. Hence, the contributions will take a closer look at epigenetic, transcriptional, posttranscriptional and posttranslational layers. Among the described regulators and transcription factors are GPX4, ACSL4 and NFE2L2. This edited volume collects reviews related to current knowledge on the integrated molecular machinery of ferroptosis, thereby also describing how dysregulated ferroptosis is involved in human diseases.

This book provides a state-of-the-art overview of key areas of subcellular aging research in human cells. The reader is introduced to the historical development and progress in biomedical aging research and learns, for example, about the role of microRNAs, circRNAs, mitochondria and extracellular vesicles in cellular senescence. The reader will also learn more about how gap junctions, the nuclear pore complex and the proteasome are affecting the ageing processes. In addition, novel therapeutic opportunities through modulation of cellular senescence are discussed. The book follows on from Parts I and II of Biochemistry and Cell Biology of Ageing (Volumes 90 and 91 of the Subcellular Biochemistry book series) by covering interesting and significant biomedical ageing topics not included in the earlier volumes. Comprehensive and cutting-edge, this book is a valuable resource for experienced researchers and early career scientist alike, who are interested in learning more about the fascinating and challenging question of why and how our cells age.

Protein Kinase Inhibitors: From Discovery to Therapeutics offers a foundational, pragmatic overview of protein kinases inhibitors and their potential role in disease modulation and treatment. Here, international experts in the field offer an integrated discussion of kinase inhibitor biology, biomarker discovery, and methods for drug design and development. After a brief overview of kinases and kinase inhibitors, subsequent chapters discuss individual kinases that are representative of the wider kinases and kinase families, including their roles in disease pathogenesis, underlying mechanisms, potential inhibitors and their modes of action for therapeutic modulation. Several potential drugs under different stages of clinical trials are discussed, including their relevance to cancer, diabetes, obesity, cardiovascular, neurological, and auto-immune and inflammatory disease, among other disorders. The book also addresses the challenges and opportunities for future kinase inhibitor development. - Provides a thorough overview of kinase inhibitor biology and its role in disease progression and modulation - Examines protein kinase inhibitor drugs in various stages of clinical trials and development - Offers methods and protocols for protein kinase inhibitor research studies and drug design and development - Includes chapter contributions from international leaders in the field

This book provides valuable coverage on various immunomodulatory research associated with nutraceutical studies, from plant to animal and marine sources. The book focuses on the various properties of nutraceutical and functional foods, from dietary fibers to fungus, marine sources, ginseng, and several others. Its content is also dedicated to the nutraceutical potential and applications of these modulators. The first section of this book focuses mainly on the recent developments in nutraceutical and functional food associated with various immunomodulators. The next section covers the micronutrients and macronutrients level in order to share important data and help readers gain a basic understanding of the techno-functional, nutraceutical potential and applications of nutritional treatment under specific disease conditions. A detailed overview providing the structural and functional properties related to immunomodulators will be highly beneficial for academics and advanced-level students in immunology, food science, clinical medicine, and life sciences.

Molecular Biology of Neurodegenerative Diseases: Visions for the Future, Part B, Volume 177 in the Progress in Molecular Biology and Translational Science series, provides the most topical, informative and exciting monographs available on a wide variety of research topics. The series includes in-depth knowledge on the molecular biological aspects of organismal physiology, with this release including chapters on Alzheimer's disease, Prion-like propagation of alpha-synuclein, What - if anything - can we learn about neurodegenerative diseases from yeast?, Mitochondrial rejuvenation and replacement as a novel strategy for treatment of age-related neurodegenerative diseases, and more. - Includes comprehensive coverage of molecular biology - Presents ample use of tables, diagrams, schemata and color figures to enhance the reader's ability to rapidly grasp the information provided - Contains contributions from renowned experts in the field

Dopamine is widely present in the central and peripheral nervous systems, as well as in non-nervous systems. Parkinson's disease is well recognized as a dopaminergic neurodegenerative disorder, and affected patients often show early signs of gastrointestinal disorders at initial stages of the disease. Apart from the changes that occur in emotion, movement behaviors, learning and memory, metabolism etc., dopamine has also been demonstrated to play very crucial roles in the functional regulation of peripheral organs such as the heart, blood vessels, kidneys, and gut. Most recently, dopamine function in the gut has received enormous attention. Not only does dopamine regulate gut motility, ion transport, and mucosal barrier, but it is becoming more pertinent that more than 60% of dopamine in the body stems from the gut, which has not yet been properly addressed and substantially explored. Therefore, this book will discuss the brain-gut axis by providing novel and significant insight into the essence of gut-derived dopamine in mammals. It aims to inspire further research on dopaminergic regulation of gut function and disease genesis.

This book offers a comprehensive exploration of research on the essential relationship of the coenzyme Q10 and the process of aging in living organisms. CoQ10 is an important factor in two main aspects of cell physiology: bioenergetics and antioxidant protection. While primary deficiency of CoQ10 is associated with severe and lethal disease, secondary deficiency can be associated with the progression of mitochondrial dysfunction linked to the lessening of biological activities during aging. The book is organized in four sections. The first offers an overview of the function of CoQ10, highlighting the two main functions of CoQ10 in cells: its essential role as electron transport chain member in mitochondria, and the protection of cell membranes against oxidation as one of the main endogenous-synthesized antioxidants. The second section covers research on Coenzyme 10. Topics include studiesinvolving invertebrate models, mammal studies and the influence of CoQ on longevity. Also covered is research involving the role of CoQ in senescence-accelerated mice. Section three examines the effects of reduced CoQ in human aging, as evident in mitochondrial dysfunction, metabolic syndrome, neurodegenerative disorders, immunosenescence and fertility and reproduction. The final section, Prolongevity effectors and Coenzyme Q, explores research into slowing or stopping the aging process. Coverage includes strategies including calorie restriction, and modulation of CoQ10 levels by induction of synthesis or by supplementation. Coenzyme Q in Aging benefits a broad readership of researchers, clinicians, educators and students interested in the biochemical and physiological effects of coenzyme Q and the importance of this molecule in aging process.

Plants produce a vast number of bioactive compounds with different chemical scaffolds, which modulate a diverse range of molecular targets and are used as drugs for treating numerous diseases. Most present-day medicines are derived either from plant compounds or their derivatives, and plant compounds continue to offer limitless reserves for the discovery of new medicines. While different classes of plant compounds, like phenolics, flavonoids, saponins and alkaloids, and their potential pharmacological applications are currently being explored, their curative mechanisms are yet to be understood in detail. This book is divided into 2 volumes and offers detailed information on plant-derived bioactive compounds, including recent research findings. Volume 1, Plant-derived Bioactives: Chemistry and Mode of Action, discusses the chemistry of highly valued plant bioactive compounds and their mode of actions at the molecular level. Volume 2, Plant-derived Bioactives: Production, Properties and Therapeutic Applications, explores the sources, biosynthesis, production, biological properties and therapeutic applications of plant bioactives. Given their scope, these books are valuable resources for members of the scientific community wishing to further explore various medicinal plants and the therapeutic applications of their bioactive compounds. They appeal to scholars, teachers and scientists involved in plant product research, and facilitate the development of innovative new drugs.

This book is the third in a series entitled, Compendium of In-Vivo Monitoring in Real-time Molecular Neuroscience. Its purpose is to provide a cross-section of research addressing monitoring in the rodent, and in some cases, the human brain.Detailed understanding of the neurobiology of the brain is demanding and involves increasingly wider scope of talent ranging from physicists, neurobiologists, chemists, molecular biologists and bioengineers. Coming from varied backgrounds, they do not necessarily understand how to formulate functional issues in a mutually understandable way. This aim of this book is to provide information which can serve as a starting point for understanding such a complex topic.The authors provide'tutorial'writing for specialists, as well as material understandable to a wide audience including neuroscientists, those interested in drug discovery, and those using such measurements for diagnosis purposes.

This book follows on from Volume 83 in the SCBI series (“Macromolecular Protein Complexes”), and addresses several important topics (such as the Proteasome, Anaphase Promoting Complex, Ribosome and Apoptosome) that were not previously included, together with a number of additional exciting topics in this rapidly expanding field of study. Although the first SCBI Protein Complex book focused on soluble protein complexes, the second (Vol. 87)addressed Membrane Complexes, and the third (Vol. 88) put the spotlight on Viral Protein and Nucleoprotein Complexes, a number of membrane, virus and even fibrillar protein complexes have been be considered for inclusion in the present book. A further book is also under preparation that follows the same pattern, in an attempt to provide a thorough coverage of the subject.Chapter 9 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

GPCRS: Structure, Function, and Drug Discovery provides a comprehensive overview of recent discoveries and our current understanding of GPCR structure, signaling, physiology, pharmacology and methods of study. In addition to the fundamental aspects of GPCR function and dynamics, international experts discuss crystal structures, GPCR complexes with partner proteins, GPCR allosteric modulation, biased signaling through protein partners, deorphanization of GPCRs, and novel GPCR-targeting ligands that could lead to the development of new therapeutics against human diseases. GPCR association with, and possible therapeutic pathways for, retinal degenerative diseases, Alzheimer's disease, Parkinson's disease, cancer and diabetic nephropathy, among other illnesses, are examined in-depth. - Addresses our current understanding and novel advances in the GPCR field, directing readers towards recent finding of key significance for translational medicine - Combines a thorough discussion of structure and function of GPCRs with disease association and drug discovery - Features chapter contributions from international experts in GPCR structure, signaling, physiology and pharmacology

Bridges the gap between the chemistry of small molecule neuromodulators and the complex pattern of neurodegenerative disorders Written by an experienced neurochemist, this book focuses on the main actors involved in neurodegenerative disorders at a molecular level, and places special emphasis on structural aspects and modes of action. Drawing on recent data on enzyme structure, mode of action, and inhibitor design, it describes?from a biochemical point of view?the six most important neurotransmitter systems and their constituent enzymes and receptors. Misfolding and aggregation of proteins within the brain is also covered. In addition, the book surveys a wide range of proven and prospective therapeutic agents that modulate key processes in the brain, from their chemical synthesis to their mode of action in model systems as well as in the patient. Chemical Biology of Neurodegeneration: A Molecular Approach is presented in two parts. The first introduces the neurotransmitter systems and provides a general explanation of the synapse and a description of the main structures involved in neurotransmission that can be considered therapeutic targets for disorders of the central nervous system. The second part presents molecular and chemical aspects directly involved or affected in neurodegeneration, including the metabolism of neurotransmitters, enzymes processing neurotransmitters, protein misfolding, and therapeutic agents. -Uses an interdisciplinary approach to bridge the gap between the basic biochemical events in a nerve cell and their neurological effects on the brain -Places emphasis on the chemistry of small molecule modulators that are potential lead molecules for new drugs -Covers six key neurotransmitter systems and their enzymes and receptors?dopaminergic, noradrenergic, serotonergic, cholinergic, GABAergic, and glutamatergic Chemical Biology of Neurodegeneration: A Molecular Approach is a key resource for medicinal chemists, neurobiologists, neurochemists, biochemists, molecular biologists, and neurophysiologists.

Protein Modificomics: From Modifications to Clinical Perspectives comprehensively deals with all of the most recent aspects of post-translational modification (PTM) of proteins, including discussions on diseases involving PTMs, such as Alzheimer's, Huntington's, X-linked spinal muscular atrophy-2, aneurysmal bone cyst, angelman syndrome and OFC10. The book also discusses the role PTMs play in plant physiology and the production of medicinally important primary and secondary metabolites. The understanding of PTMs in plants helps us enhance the production of these metabolites without greatly altering the genome, providing robust eukaryotic systems for the production and isolation of desired products without considerable downstream and isolation processes. - Provides thorough insights into the post translational modifications (PTMs) of proteins in both the plant and animal kingdom - Presents diagrammatic representations of various protein modification and estimation mechanisms in four-color - Includes coverage of diseases involving post translational modifications

This book, now in an extensively revised second edition, describes the crucial role of zinc signaling in biological processes on a molecular and physiological basis. Global leaders in the field review the latest knowledge, including the very significant advances in understanding that have been achieved since publication of the first edition. Detailed information is provided on all the essentials of zinc signaling, covering molecular aspects and the roles of zinc transporters, the zinc sensing receptor, and metallothioneins. Detection techniques for zinc signals, involving genetically encoded and chemical probes, are also described. The critical contributions of the zinc signal in maintaining health and the adverse consequences of any imbalance in the signal are then thoroughly addressed. Here, readers will find up-to-date information on the significance of the zinc signal in a wide range of conditions, including cardiovascular disorders, neurodegenerative diseases, diabetes,autoimmune diseases, inflammatory conditions, skin disease, osteoarthritis, and cancer. The book will be of value for researchers, clinicians, and advanced students.

This book sheds new light on ferroptosis, as an only recently recognised form of regulated cell death. Its respective chapters address the numerous implications that ferroptosis can have for virtually all aspects of metabolism. They also share insights on the morphological characterisation of ferroptosis and highlight the different pathways of induction. Accordingly, the book offers a unique perspective on a mechanism that is involved in a multitude of pathologies, including cancer cell death, neurotoxicity, neurodegenerative diseases, acute renal failure, drug-induced hepatotoxicity, tissue ischemia/reperfusion injury, and T cell immunity. Readers will learn in which cell types this form of regulated cell death is likely to occur, and how it can be pharmacologically influenced, making the book a fascinating and informative read not only for scientists working in cell biology, but also for clinicians in the field of cancer research.

This book presents essential studies and cutting-edge research results on tau, which is attracting increasing interest as a target for the treatment of Alzheimer's disease. Tau is well known as a microtubule-associated protein that is predominantly localized in the axons of neurons. In various forms of brain disease, neuronal loss occurs, with deposition of hyperphosphorylated tau in the remaining neurons. Important questions remain regarding the way in which tau forms hyperphosphorylated and fibrillar deposits in neurons, and whether tau aggregation represents the toxic pathway leading to neuronal death. With the help of new technologies, researchers are now solving these long-standing questions. In this book, readers will find the latest expert knowledge on all aspects of tau biology, including the structure and role of the tau molecule, tau localization and function, the pathology, drivers, and markers of tauopathies, tau aggregation, and treatments targeting tau. Tau Biology will be an invaluable source of information and fresh ideas for those involved in the development of more effective therapies and for all who seek a better understanding of the biology of the aging brain.

The Organizing Committee of the 15th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases compiled a group of junior investigators to provide reviews on the topics they presented at the Puerto Vallarta Bioactive Lipids conference, as part of the book series, Advances in Experimental Medicine and Biology (AEMB). The book in this series will be titled Bioactive Lipids in Cancer, Inflammation and Related Diseases. Topics range from all classes of lipids including prostaglandins, resolvins, spingolipids, P450-derived lipids, endocannabanoids and phospholipids. The focus includes physiology, cell biology, and structural studies in organisms from bacteria to humans and how these studies addressed the role of lipids in various disease i.e. cancer, inflammation, diabetes, obesity, cardiovascular disease and others.

Parkinson's Disease is the second most common neurodegenerative disorder affecting millions of people worldwide. In order to find neuroprotective strategies, a clear understanding of the mechanisms involved in the dopaminergic death of cells that progresses the disease is needed. Oxidative stress can be defined as an imbalance between the production of reactive species and the ability to detoxify them and their intermediates or by-products. Oxidative damage to lipids, proteins, and DNA has been detected in autopsies from individuals with Parkinson's Disease and so links can be made between oxidative stress and Parkinson's Disease pathogenesis.This book provides a thorough review of the mechanisms by which oxidative stress and redox signalling mediate Parkinson's Disease. Opening chapters bring readers up to speed on basic knowledge regarding oxidative stress and redox signalling, Parkinson's Disease, and neurodegeneration before the latest advances in this field are explored in detail. Topics covered in the following chapters include the role of mitochondria, dopamine metabolism, metal homeostasis, inflammation, DNA-damage and thiol-signalling. The role of genetics and gene-environment interactions are also explored before final chapters discuss the identification of potential biomarkers for diagnosis and disease progression and the future of redox/antioxidant based therapeutics.Written by recognized experts in the field, this book will be a valuable source of information for postgraduate students and academics, clinicians, toxicologists and risk assessment groups. Importantly, it presents the current research that might later lead to redox or antioxidant – based therapeutics for Parkinson's disease.

Leveraging Biomedical and Healthcare Data: Semantics, Analytics and Knowledge provides an overview of the approaches used in semantic systems biology, introduces novel areas of its application, and describes step-wise protocols for transforming heterogeneous data into useful knowledge that can influence healthcare and biomedical research. Given the astronomical increase in the number of published reports, papers, and datasets over the last few decades, the ability to curate this data has become a new field of biomedical and healthcare research. This book discusses big data text-based mining to better understand the molecular architecture of diseases and to guide health care decision. It will be a valuable resource for bioinformaticians and members of several areas of the biomedical field who are interested in understanding more about how to process and apply great amounts of data to improve their research. - Includes at each section resource pages containing a list of available curated raw and processed data that can be used by researchers in the field - Provides demonstrative and relevant examples that serve as a general tutorial - Presents a list of algorithm names and computational tools available for basic and clinical researchers

Global health and the increasing incidence of various diseases are a cause for concern, and doctors and scientists reason that the diet, food habits and lifestyle are contributing factors. Processed food has reduced the nutritional value of our diet, and although supplementing foods with various additives is considered an alternative, the long-term impact of this is not known. Many laboratories around the world are working to identify various nutritional components in our daily food and their effect on human health. These have been classified as Nutraceuticals or functional food, and they may have preventive and therapeutic effects in a number of pathologies associated with modern dietary habits and lifestyles. This book addresses various aspects of this issue, revitalizing the discussion and consolidating the latest research on nutritional and functional food and their effects in in-vitro, in-vivo and human clinical studies.

This book provides an essential overview of the rapidly advancing field of circular RNAs – newly discovered RNAs that are generated by back-splicing precursor mRNA and perform regulatory functions in many biological processes. Although many aspects of circular RNAs'biology and mechanisms of gene regulation remain unclear, they have been found to be abundant, evolutionally conserved, and stable in cells; further, they have numerous potential functions. The book consists of eight parts:1) An overview of circular RNAs, 2) Bioinformatics for circular RNAs, 3) Biogenesis of circular RNAs, 4) Molecular mechanisms and gene regulation of circular RNAs, 5) Circular RNAs as potential disease biomarkers, 6) Circular RNAs and human diseases, 7) Circular RNAs in Plants and in Archaea, and 8) Future prospects. Given its focus, the book will be especially useful for researchers and students in the fields of biochemistry, molecular biology, cell biology, and medicine.

This volume on iron-sulfur proteins includes chapters that discuss how microbes, plants, and animals synthesize these complex prosthetic groups, and why it is important to understand the chemistry and biogenesis of iron sulfur proteins. In addition to their vital importance in mitochondrial respiration, numerous iron sulfur proteins are important in maintenance of DNA integrity. Multiple rare human diseases with different clinical presentations are caused by mutations of genes in the iron sulfur cluster biogenesis pathway. Understanding iron sulfur proteins is important for understanding a rapidly expanding group of metabolic pathways important in all kingdoms of life, and for understanding processes ranging from nitrogen fixation to human disease.

This ​book provides a comprehensive overview on current histamine and histamine receptor research in context of human health and disease and reflect the multidisciplinary nature of the field. While the editors realize that it is almost impossible to cover the field completely within the constraints of a single HEP volume, nonetheless, all important aspects will be covered in one way or the other. An overarching introductory chapter will link the individual chapters and provide an overview on the field. This chapter will also link the book to the previous HEP volume on histamine receptors and the recent HEP volume on the pharmacology of itch. Great attention will be paid to complementation of existing literature while avoiding undue duplication. The book will cover new methods for analysis of histamine and histamine metabolites, development of methods for histamine receptor analysis, signal transduction, histamine release, regulation of immune cells by histamine, histamine metabolism and associated diseases, regulation of major organ systems by histamine and development of new drugs and experimental tools for the study of histamine receptors.

This book provides the first comprehensive coverage of the quickly evolving research field of membrane contact sites (MCS). A total of 16 chapters explain their organization and role and unveil the significance of MCS for various diseases. MCS, the intracellular structures where organellar membranes come in close contact with one another, mediate the exchange of proteins, lipids, and ions. Via these functions, MCS are critical for the survival and the growth of the cell. Owing to that central role in the functioning of cells, MCS dysfunctions lead to important defects of human physiology, influence viral and bacterial infection, and cause disease such as inflammation, type II diabetes, neurodegenerative disorders, and cancer. To approach such a multifaceted topic, this volume assembles a series of chapters dealing with the full array of research about MCS and their respective roles for diseases. Most chapters also introduce the history and the state of the art ofMCS research, which will initiate discussion points for the respective types of MCS for years to come. This work will appeal to all cell biologists as well as researchers on diseases that are impacted by MCS dysfunction. Additionally, it will stimulate graduate students and postdocs who will energize, drive, and develop the research field in the near future.

Although the concept of allosterism has been known for over half a century, its application in drug discovery has exploded in recent years. The emergence of novel technologies that enable molecular-level ligand-receptor interactions to be studied in studied in unprecedented detail has driven this trend. This book, written by the leaders in this young research area, describes the latest developments in allosterism for drug discovery. Bringing together research in a diverse range of scientific disciplines, Allosterism in Drug Discovery is a key reference for academics and industrialists interested in understanding allosteric interactions. The book provides an in-depth review of research using small molecules as chemical probes and drug candidates that interact allosterically with proteins of relevance to life sciences and human disease. Knowledge of these interactions can then be applied in the discovery of the novel therapeutics of the future. This book will be useful for people working in all disciplines associated with drug discovery in academia or industry, as well as postgraduate students who may be working in the design of allosteric modulators.

This book reviews the functions and roles of DJ-1 in various oxidative stress-related diseases and applications of DJ-1 and its binding compounds to the diseases. The DJ-1 gene was first found to be a novel oncogene in 1997 and later, in 2003, also found to be a causative gene for a familial form of Parkinson's disease (PD), park7. The DJ-1 gene is therefore the first gene discovered that is known to cause cancer and neurodenegerative diseases, including PD. The research field has expanded as the research has developed. Thus this volume begins with a general introduction of DJ-1, and explains the history and research development to understand the following chapters. Those chapters present the roles of DJ-1 in various oxidative stress-related diseases such as neurodegenerative diseases, as well as cancer, diabetes, and fertility. Moreover, several chapters present evidence that DJ-1 is useful for therapeutic strategies against these diseases. The reader willdiscover that DJ-1 is a promising protein both for basic cell biology and for the mechanism and therapy for oxidative stress-related diseases.

Epigenetic mechanisms (DNA modifications, histone alterations and non-coding RNAs) are crucial for transcriptional regulation and alterations of the “physiological epigenome” are increasingly associated with human diseases. During the last decade the emerging field of neuroepigenomics have started to impact tremendously in areas such learning and memory, addiction or neurodegeneration. This expert volume covers the role of epigenetic molecular mechanism in regulation of central nervous system's function, one of the most exciting areas of contemporary molecular neuroscience. The book describes the current knowledge on the epigenetic basis of human disease covering the complete lifespan: from neurodevelopment/childhood (Rett Syndrome, Rubinstein-Taybi, autism), adolescence (eating disorders, drug addiction, anxiety), adulthood (depression, schizophrenia, amyotrophic lateral sclerosis, Huntington's disease) and elderly (Alzheimer's disease, Parkinson's disease). The book also covers the three major players on neuroepigenomic mechanisms: histones alterations, DNA modifications and non-coding RNAs, their roles at the molecular and cellular level and the impact of their alterations on neuronal function and behavior. Finally, a special chapter on state-of-the-art technologies helps the reader not only to understand epigenetic driven changes in human cognition and diseases but also the methodology that will help to generate paradigm shifts on our understanding of brain function and the role of the neuroepigenome in human diseases.

This book highlights the latest international research on different aspects of medicinal plants and fungi. Studies over the last decade have demonstrated that bioactive compounds isolated from medicinal fungi have promising antitumor, cardiovascular, immunomodulatory, anti-allergic, anti-diabetic, and hepatoprotective properties. In the light of these studies, the book includes chapters (mostly review articles) by eminent researchers from twelve countries across the globe working in different disciplines of medicinal plants and fungi. It discusses topics such as the prevention of major neurodegenerative and neurotoxic mechanisms by Centella asiatica; the medicinal properties and therapeutic applications of several mushrooms species found in different parts of the world; and fungal endophytes as a source of bioactive metabolites including anticancer and cardioprotective agents. There are also chapters on strategies for identifying bioactive secondary metabolitesof fungal origin; the use of genomic information to explore the biotechnological potential of medicinal mushrooms; and solid state fermentation of agro-industrial and forestry residues for the production of medicinal mushrooms. It is a valuable resource for the researchers, professionals and students working in the area of medicinal plants and fungi.

This PIR volume presents a comprehensive collection of reviews that focus on the role of the blood-brain barrier (BBB) during steady-state and inflamed conditions. Within the central nervous system (CNS) the constantly changing bloodstream is strictly separated from the CNS parenchyma by the BBB. However, viruses, bacteria, parasites and auto-aggressive immune cells can penetrate the barrier and significantly contribute to CNS inflammation. The BBB can actively contribute to neuroinflammation by presentation of chemokines, expression of cell adhesion molecules and alterations of barrier properties. As such, understanding the role of the BBB under healthy and pathological conditions is essential to the development of new drugs to efficiently combat inflammatory diseases of the CNS.

Metal chelators are emerging as versatile tool with many medical applications. Their versatility allows them to be used in chelation therapy for treating diseases caused by toxic and heavy metal poisoning, chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. In addition, metal chelators can also be applied as contrast agents in MRI scanning. Metal Chelation in Medicine provides a clear and timely perspective on the role of chelating agents in the management of metal intoxications and storage diseases. Written by leaders in the field of chelators, this publication is at the cutting-edge of the subject. It covers a broad range of topics such as the use of metal chelators in non-invasive assessment of brain iron overload, and the treatment of systemic iron overload and neurodegenerative diseases. As such it is particularly valuable to clinicians treating metal poisonings and metal storage diseases. However, it is also a useful text for researchers, industry professionals and university students with a specific interest in medicinal chemistry, chelation, metal ions, imaging and non-invasive techniques.

This book is about “Angiogenesis”. A process in which new vasculature is formed from pre-existing capillaries. Angiogenesis process is associated with the proliferation and growth of both physiologically normal and neoplastic tissues, through the formation of vascular supply, essential for delivering growth requirements such as oxygen and nutrients.The book describes more than 100 genes and their key regulatory functions in the context of normal healthy condition, disease and malignancy, cancer proliferation and progression. New insights into the role of angiogenesis and the therapeutic inhibition of its regulators are investigated, due to the great potential for exploitation in the development of a novel treatment for cancer.New scientists, junior researchers and biomedical science students will find this book an invaluable introductory reference to their insight about angiogenesis and angiogenic role of more than 100 angiogenes and their role in healthy, disease and malignant conditions.

Sphingolipids are involved in a wide range of physiological and pathological processes none only s signaling molecules but also as key structural components regulating the lateral organization of cellular membranes. In this book, exciting new approaches that open a window to further characterize sphingolipid-enriched domains in cell membranes during both physiological and pathological processes are reviewed. Furthermore, sphingolipids (SLs) are especially important in the central nervous system (CNS) where they are a necessary structural component of membranes of brain cells or signaling molecules. Ceramides are the core constituent of most sphingolipids. The authors review the possible sources of ceramides in the central nervous system (CNS) and present information about recent preclinical clinical trials of therapies targeting the ceramide pathway in the brain. Data about significant alteration in levels of ceramides in brain cells during the development of different neurodegenerative disease are also discussed, such as in with Alzheimer's disease, Parkinson's disease multiple sclerosis, cerebral ischemia, Gaucher's and Farber's disease.

These new volumes of Methods in Enzymology (554 and 555) on Hydrogen Sulfide Signaling continue the legacy established by previous volumes on another gasotransmitter, nitric oxide (Methods in Enzymology volumes 359, 396, 440, and 441), with quality chapters authored by leaders in the field of hydrogen sulfide research. These volumes of Methods in Enzymology were designed as a compendium for hydrogen sulfide detection methods, the pharmacological activity of hydrogen sulfide donors, the redox biochemistry of hydrogen sulfide and its metabolism in mammalian tissues, the mechanisms inherent in hydrogen sulfide cell signaling and transcriptional pathways, and cell signaling in specific systems, such as cardiovascular and nervous system as well as its function in inflammatory responses. Two chapters are also devoted to hydrogen sulfide in plants and a newcomer, molecular hydrogen, its function as a novel antioxidant. - Continues the legacy of this premier serial with quality chapters on hydrogen sulfide research authored by leaders in the field - Covers conventional and new hydrogen sulfide detection methods - Covers the pharmacological activity of hydrogen sulfide donors - Contains chapters on important topics on hydrogen sulfide modulation of cell signaling and transcriptional pathways, and the the role of hydrogen sulfide in the cardiovascular and nervous systems and in inflammation

Manganese in the diet is nutritionally essential for normal physiologic functioning. However, excessive exposure to manganese has been associated with developmental, neurodegenerative and other disorders. The book comprehensively covers the toxicology of manganese. Leading investigators provide perspectives from toxicology, neuroscience, nutrition, molecular biology and risk assessment disciplines and chapters cover the toxicokinetics, toxicodynamic interactions and health effects of manganese, as well as its potential role in neurodegenerative diseases. A large section devoted to health effects presents the latest research that associates manganese exposure to potential human diseases. Any scientists, health professional or regulator involved with metal exposure and toxicology should find this volume essential reading. Students and researchers in neurotoxicology will also find this book a useful reference.

Bio-Nanoimaging: Protein Misfolding & Aggregation provides a unique introduction to both novel and established nanoimaging techniques for visualization and characterization of misfolded and aggregated protein species. The book is divided into three sections covering:- Nanotechnology and nanoimaging technology, including cryoelectron microscopy of beta(2)-microglobulin, studying amyloidogensis by FRET; and scanning tunneling microscopy of protein deposits - Polymorphisms of protein misfolded and aggregated species, including fibrillar polymorphism, amyloid-like protofibrils, and insulin oligomers- Polymorphisms of misfolding and aggregation processes, including multiple pathways of lysozyme aggregation, misfolded intermediate of a PDZ domain, and micelle formation by human islet amyloid polypeptide Protein misfolding and aggregation is a fast-growing frontier in molecular medicine and protein chemistry. Related disorders include cataracts, arthritis, cystic fibrosis, late-onset diabetes mellitus, and numerous neurodegenerative diseases like Alzheimer's and Parkinson's. Nanoimaging technology has proved crucial in understanding protein-misfolding pathologies and in potential drug design aimed at the inhibition or reversal of protein aggregation. Using these technologies, researchers can monitor the aggregation process, visualize protein aggregates and analyze their properties. - Provides practical examples of nanoimaging research from leading molecular biology, cell biology, protein chemistry, biotechnology, genetics, and pharmaceutical labs - Includes over 200 color images to illustrate the power of various nanoimaging technologies - Focuses on nanoimaging techniques applied to protein misfolding and aggregation in molecular medicine

Affecting over 1.5 million people across the world, Parkinson's disease is a progressive neurological condition characterized, in part, by the loss of dopaminergic neurons in the substantia nigra pars compacta. It affects 1.5% of the global population over 65 years of age. As life expectancy is increasing, over the next few years the number of patients with Parkinson´s disease will grow exponentially. To date, there are no available treatments that are capable of curing Parkinson´s disease, and the current goal of therapy, dopamine replacement strategies, is to reduce symptoms. After several years of disease progression, treatment is complicated by the onset of motor fluctuations and dyskinesias. This information reveals the great importance and social need of finding an effective therapeutic intervention for Parkinson´s disease. This exemplary new book reviews some of the most outstanding examples of new drugs currently in pharmaceutical development or new targets currently undergoing the validation process to try to reach the Parkinson´s drug market in the next few years as potential disease modifying drugs. Providing up to date and comprehensive coverage, this book is essential reading for researchers working in academia and industry in any aspect of medicinal chemistry or drug discovery.

Proceedings of the Fifteenth Washington International Spring Symposium held at The George Washington University, Washington, D.C., May 15-17, 1995

The past few years have seen rapid progress in apoptosis research. This volume deals with many of the recent advances made in uncovering the molecular and cellular basis of apoptosis and elaborates on how this accumulating knowledge is helping us to understand the significance of apoptosis in pathogenesis of diseases arising from inappropriate cell death. Further, mechanistic aspects of cell death and role of apoptosis in disease is covered. The articles published in this volume are written by leading experts in the field and should be a vital resource for researchers in biomedicine and cancer research.

Internationally eminent scientists illuminate the most important scientific aspects of essential fatty acids (EFAs)-from their biochemistry to their physiological consequences in both health and illness. The distinguished contributors integrate a wide range of topics, including the basic biochemistry of EFAs and lipid metabolism, the role of EFAs in the neuronal membrane, the effects of EFAs and lipids in various diseases, and the effects of normal levels and EFA deficiencies on cognition and behavior. The book's consolidation of our knowledge of the biology and metabolism of the EFAs lays the groundwork for dramatic advances in our understanding of these ubiquitous biochemicals and their role in health and illness.

Among the various theories proposed to account for the process of aging, the free radical theory is of practical interest since it includes the possibility of retarding this process by administrating natural or synthetic antioxidants and free radical scavengers. The book'Free Radicals and Aging'summarizes knowledge accumulated during recent years in 42 reviews written by experts in the field. Aspects of free radical involvement in the intrinsic aging process and in age-related diseases, as well as the importance of the pro-antioxidant balance throughout life are discussed. Epidemiological studies from several European countries are reported showing correlations between low plasma levels of essential antioxidants and the occurence of coronary heart disease, cancer and cataract formation. Appropriate nutrition as well as prophylactic and therapeutic use of antioxidants are considered. This book represents a milestone in the field of age-related free radical biology and medicine. With contributions by: A. Azzi, B. Chance, R.G. Cutler, H. Esterbauer, P.H. Evans, F. Gey, C. Guarneri, D. Harman, N.I. Krinsky, M. Meydani, J. Miquel, A. Mori, L. Packer, C. Rice-Evans, M. Simic, A. Taylor, T. Yoshikawa.

Band 1 beinhaltet grundlegende theoretische und therapeutische Aspekte der Psychopharmakotherapie. Neben einem historischen Abriß werden die Arzt-Patient-Beziehung, Nutzen und Risiken sowie ethische Aspekte der Pharmakopsychiatrie dargelegt. Die theoretischen Grundlagen von Tierexperimenten, präklinischen Humanversuchen, der Pharmakopsychologie, des Pharmako-EEGs, der Psychometrie und Skalierung, des Placebo-Problems sowie der Effizienz-Kontrolle und die Durchführung klinischer Studien werden dargestellt. Des weiteren werden juristische Aspekte sowie Ergebnisse der Compliance-Forschung wiedergegeben. Grundlagenkapitel beleuchten molekulare Grundlagen, Wirkmechanismen, Aspekte der Pharmakogenetik sowie Basiswissen der Pharmakokinetik. Die Perspektive der Praxis findet in den Kapiteln Verbrauchsstatistik, Psychopharmaka und Fahrtauglichkeit, Psychopharmaka und Schwangerschaft sowie in den Abschnitten Psychopharmaka bei Kindern/Jugendlichen bzw. im höheren Lebensalter Berücksichtigung. Gesondert wird auf die Probleme Abusus und Abhängigkeit, kombinierte Psychopharmakotherapie sowie Prädiktoren für das Ansprechen auf Psychopharmaka eingegangen. Der Band schließt mit einem Kapitel über die statistische Auswertung von Psychopharmaka-Prüfstudien.