Structure-Based Drug Design for Diagnosis and Treatment of Neurological Diseases


Book Description

European Cooperation in Science and Technology (COST) supports the collaboration of nationally-funded science and technology research through the creation of networks. COST is the longest-running European framework enhancing cooperation among researchers, engineers and scholars across Europe. The COST Action CM1103 “Structure-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain” is a good example of the advances possible through interdisciplinary collaboration on difficult problems. COST Action CM1103 brought together 28 research groups from 18 countries to collaborate for four years on multi-target drug design for complex neuropathologies. The interdisciplinary expertise of the members is spans the range from computational enzymology to human studies, providing outstanding opportunities for the interdisciplinary development of trainees, and is reflected in the articles in this e-book. This Research Topic covers progress in multi-target drug design for the complex neuropathologies of the monoamine system that are apparent, for example, in Alzheimer’s disease. After a mini-review to introduce the topic of multi-target drug design, the other articles review the Research topic from their own perspective, two from computational approaches, three from medicinal chemistry, two from molecular pharmacology, and two from studies in whole brain. This multi-faceted approach describes new compounds, new methodology, and advances in the basic science of understanding the brain. This Ebook is based upon work from COST Action (CM1103 “Structure-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain"), supported by COST (European Cooperation in Science and Technology). COST (European Cooperation in Science and Technology) is a pan-European intergovernmental framework. Its mission is to enable break-through scientific and technological developments leading to new concepts and products and thereby contribute to strengthening Europe’s research and innovation capacities. It allows researchers, engineers and scholars to jointly develop their own ideas and take new initiatives across all fields of science and technology, while promoting multi- and interdisciplinary approaches. COST aims at fostering a better integration of less research intensive countries to the knowledge hubs of the European Research Area. The COST Association, an International not-for-profit Association under Belgian Law, integrates all management, governing and administrative functions necessary for the operation of the framework. The COST Association has currently 36 Member Countries. www.cost.eu




Improving and Accelerating Therapeutic Development for Nervous System Disorders


Book Description

Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.




Drug Design and Discovery in Alzheimer's Disease


Book Description

Drug Design and Discovery in Alzheimer's Disease includes expert reviews of recent developments in Alzheimer's disease (AD) and neurodegenerative disease research. Originally published by Bentham as Frontiers in Drug Design and Discovery, Volume 6and now distributed by Elsevier, this compilation of the sixteen articles, written by leading global researchers, focuses on key developments in the understanding of the disease at molecular levels, identification and validation of molecular targets, as well as innovative approaches towards drug discovery, development, and delivery. Beginning with an overview of AD pharmacotherapy and existing blockbuster drugs, the reviews cover the potential of both natural and synthetic small molecules; the role of cholinesterases in the on-set and progression of AD and their inhibition; the role of beta-site APP clearing enzyme-1 (BACE-1) in the production of ß-amyloid proteins, one of the key reasons of the progression of AD; and other targets identified for AD drug discovery. - Edited and written by leading experts in Alzheimer's disease (AD) and other neurodegenerative disease drug development - Describes existing drugs for AD and current molecular understanding of the condition - Reviews recent advances in the field, including coverage of cholinesterases, BACE-1, and other drug development targets




Drugs in Neurology


Book Description

Part of the Drugs in series, this book provides an easily accessible pocket-sized guide to the use of medications when treating patients with neurological ailments. Drugs in Neurology covers the breadth of medications used in modern neurology, including each drug's indications, contra-indications, side-effects and important interactions. The underlying pharmacology also feature (where known). Practical aspects related to prescribing and therapeutic drug monitoring are covered and based on the most up-to-date evidence-based guidance. Each drug monograph contains a small section drawing on the wisdom of the senior contributors of each chapter with regards to using the medication.




Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders


Book Description

Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders: Alzheimer's Disease examines the drug discovery process for neurodegenerative diseases by focusing specifically on Alzheimer's Disease and illustrating the paradigm necessary to ensure future research and treatment success. The book explores diagnosis, epidemiology, drug discovery strategies, current therapeutics, and much more to provide a holistic approach to the discovery, development, and treatment of Alzheimer's Disease. Through its coverage of the latest research in targeted drug design, preclinical studies, and mouse and rat models, the book is a must-have resource for all pharmaceutical scientists, pharmacologists, neuroscientists, and clinical researchers working in this area. It illustrates why these drugs tend to fail at the clinical stage, and examines Alzheimer's Disease within the overall context of improving the drug discovery process for the treatment of other neurodegenerative disorders. - Provides a compilation of chemical considerations required in drug discovery for the treatment of neurodegenerative disorders - Examines different classes of compounds currently being used in discovery and development stages - Explores in vitro and in vivo models with respect to their ability to translate these models to human conditions - Distills the most significant information across multiple areas of Alzheimer's disease research to provide a single, comprehensive, and balanced resource




Disease Control Priorities, Third Edition (Volume 4)


Book Description

Mental, neurological, and substance use disorders are common, highly disabling, and associated with significant premature mortality. The impact of these disorders on the social and economic well-being of individuals, families, and societies is large, growing, and underestimated. Despite this burden, these disorders have been systematically neglected, particularly in low- and middle-income countries, with pitifully small contributions to scaling up cost-effective prevention and treatment strategies. Systematically compiling the substantial existing knowledge to address this inequity is the central goal of this volume. This evidence-base can help policy makers in resource-constrained settings as they prioritize programs and interventions to address these disorders.




Structure-Based Drug Discovery


Book Description

The last decade has seen the confluence of several enabling technologies that have allowed protein crystallographic methods to live up to their true potential. Taken together, the numerous recent advances have made it possible to tackle difficult biological targets with a high probability of success: intact bacterial ribosomes have been structurally elucidated, as well as eukaryotic trans-membrane proteins like the potassium channel and GPCRs. It is now possible for medicinal chemists to have access to structural information on their latest small molecule candidates bound to the therapeutic target within days of compound synthesis, allowing structure guided ligand optimization to occur in "real time". Structure-Based Drug Discovery presents an array of methods used to generate crystal structures of biological macromolecules, how to leverage the structural information to design novel ligands anew, and how to iteratively optimize hits and convert them to leads. Written in the successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Structure-Based Drug Discovery aims to provide scientists interested in adding SBDD to their arsenal of drug discovery methods with well-honed, up-to-date methodologies.




Computer-Aided Drug Design


Book Description

This book provides up-to-date information on bioinformatics tools for the discovery and development of new drug molecules. It discusses a range of computational applications, including three-dimensional modeling of protein structures, protein-ligand docking, and molecular dynamics simulation of protein-ligand complexes for identifying desirable drug candidates. It also explores computational approaches for identifying potential drug targets and for pharmacophore modeling. Moreover, it presents structure- and ligand-based drug design tools to optimize known drugs and guide the design of new molecules. The book also describes methods for identifying small-molecule binding pockets in proteins, and summarizes the databases used to explore the essential properties of drugs, drug-like small molecules and their targets. In addition, the book highlights various tools to predict the absorption, distribution, metabolism, excretion (ADME) and toxicity (T) of potential drug candidates. Lastly, it reviews in silico tools that can facilitate vaccine design and discusses their limitations.




Beyond the Molecular Frontier


Book Description

Chemistry and chemical engineering have changed significantly in the last decade. They have broadened their scopeâ€"into biology, nanotechnology, materials science, computation, and advanced methods of process systems engineering and controlâ€"so much that the programs in most chemistry and chemical engineering departments now barely resemble the classical notion of chemistry. Beyond the Molecular Frontier brings together research, discovery, and invention across the entire spectrum of the chemical sciencesâ€"from fundamental, molecular-level chemistry to large-scale chemical processing technology. This reflects the way the field has evolved, the synergy at universities between research and education in chemistry and chemical engineering, and the way chemists and chemical engineers work together in industry. The astonishing developments in science and engineering during the 20th century have made it possible to dream of new goals that might previously have been considered unthinkable. This book identifies the key opportunities and challenges for the chemical sciences, from basic research to societal needs and from terrorism defense to environmental protection, and it looks at the ways in which chemists and chemical engineers can work together to contribute to an improved future.




Functional Neurologic Disorders


Book Description

Functional Neurologic Disorders, the latest volume in the Handbook of Clinical Neurology series, summarizes state-of-the-art research findings and clinical practice on this class of disorders at the interface between neurology and psychiatry. This 51-chapter volume offers an historical introduction, chapters on epidemiology and pathophysiolology, a large section on the clinical features of different type of functional neurologic symptoms and disorders (including functional movement disorders, non-epileptic seizures, dizziness, vision, hearing, speech and cognitive symptoms), and then concluding with approaches to therapy. This group of internationally acclaimed experts in neurology, psychiatry, and neuroscience represent a broad spectrum of areas of expertise, chosen for their ability to write clearly and concisely with an eye toward a clinical audience. This HCN volume sets a new landmark standard for a comprehensive, multi-authored work dealing with functional neurologic disorders (also described as psychogenic, dissociative or conversion disorders). - Offers a comprehensive interdisciplinary approach for the care of patients with functional disorders seen in neurologic practice, leading to more efficient prevention, management, and treatment - Provides a synthesis of research efforts incorporating clinical, brain imaging and neurophysiological studies - Fills an existing gap between traditional neurology and traditional psychiatry - Contents include coverage of history, epidemiology, clinical presentations, and therapy - Edited work with chapters authored by leaders in the field, the broadest, most expert coverage available