Receptor Tyrosine Kinases In Neurodegenerative And Psychiatric Disorders

Overexpression of receptor tyrosine kinases (RTKs) has been implicated in cancer. Increasing evidence suggests that dysregulation of RTKs is reported in many neurodegenerative and psychiatric disorders. Receptor Tyrosine Kinases in Neurodegenerative and Psychiatric Disorders provides a fundamental, pragmatic map of RTKs structure, activation, functions, mechanism of action, gene regulation, and signaling pathways in developing central nervous system (CNS), adult normal CNS, neurodegenerative and psychiatric disorders. Additionally, the structure, function, activation, and therapeutic potential of many growth factors have been covered. Here, international experts in the field offer a comprehensive discussion of results of pre-clinical and clinical studies of repositioning of anti-cancer receptor tyrosine kinase inhibitors (RTKIs) and other promising protein kinase inhibitors in various neurodegenerative disorders including, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis, and psychiatric disorders including, anxiety, depression, alcohol use disorder, and schizophrenia. In addition, the book discusses the obstacles and opportunities for the potential repositioning of kinase inhibitors in neurodegenerative and psychiatric disorders. Provides a thorough overview of RTKs biology and their role in health and disease progression and modulation Highlights RTK families and the numerous receptors within each subfamily Examines RTKIs and other protein kinase inhibitors in pre-clinical and clinical trials in both neurodegenerative and psychiatric disorders Gives future directions of possible safe effective targeted RTKIs and other protein kinase inhibitors that may be repositioned in various neurodegenerative and psychiatric disorders Includes chapter contributions from renowned experts in biology, pharmacology, neurology, psychiatry, and oncology

This book devotes a chapter to each RTK family and the multiple receptors within each family, thoroughly covering all of the RTKs. The chapters all follow the same structure, presenting this essential information in an accessible and user-friendly format. Each chapter covers one specific family of receptors and begins with a general introduction to that family and a comprehensive discussion of that receptor’s family in development and human disease. Following are in-depth analyses of each family’s receptors with discussions on the gene, protein, ligands, activation, and signaling pathways along with discussion of receptor processing and signal attenuation. Further, cross talk with other receptors systems, post-translational modification and specific unique characteristics to each RTK are discussed. Because it isolates and explains each family, this book is an essential companion volume to Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease, by the same authors, which talks about RTKs more generally and without the family-by-family detail.

Successful management of patients with treatment-resistant depression is going to require a thorough understanding of the biological basis for both the depression and its failure to respond to standard treatments. This book clearly and succinctly summarizes the latest scientific research and its applications in clinical practice. A first step is a clear definition of what constitutes treatment-resistant depression so that clinical trials and other studies are using common criteria, enabling comparison and meta-analysis of their outcomes. The opening chapter reviews definitions and predictors of originating from different fields and discusses their usefulness in clinical practice and clinical research. The next chapter proposes a new definition, adapting terminology from medicine. Biological classification requires identification of genetic risk factors: with gene variants accounting for 50% of the variance in the clinical outcomes of antidepressant treatments this is clearly a fruitful area of research. Chapter 3 describes several genes already associated with treatment-resistant depression and, while further work is needed to translate findings into clinical recommendations, predicts that genetic prediction of TRD could became a widespread clinical reality within a few years. Most patients with TRD will be treated pharmacologically and three chapters review the latest evidence for pharmacological best practice, including switching strategies for antidepressants, the role of antipsychotics and augmentation strategies to complement lithium. There are two major alternatives to pharmacotherapy: neuromodulation and psychotherapy. The brain intervention chapter summarizes clinical research and experience with electroconvulsive therapy, transcranial magnetic stimulation, vagus nerve stimulation, deep brain stimulation and magnetic seizure therapy. The final chapter reviews the literature pertaining to the effectiveness of various forms of psychotherapy in patients who have not responded to antidepressant pharmacotherapy, revealing that patients who have not responded to one or two trials of antidepressant medication have a 30%-50% chance of responding to a focused psychotherapy. It proposes indications for psychotherapy in TRD and summarizes general therapeutic principles.

Adverse Events and Oncotargeted Kinase Inhibitors gathers and evaluates data on adverse events associated with tyrosine kinase inhibitors (TKIs), a powerful anti-tumor drug class that has recently been introduced for human therapy. This book compiles a comprehensive safety profile of each TKI from experiences in official therapeutic indications, also exploring off-label exploratory investigations and postmarketing pharmaceutical surveillance databases. A brief history of each drug’s development and submission is provided, along with a more detailed analysis of the mechanism(s) of action involved in therapeutic activity or related to the insurgence of specific adverse events. Early chapters focus on general characteristics of TKIs, typology, and classification of adverse events, while the final chapters analyze TKIs as AE inducers and classes of AEs by system or organ involvement. This comprehensive resource compiles and critically reviews all of the relevant safety data for this class of drugs, with the goal of improving the understanding of pathogenesis and facilitating the prevention, monitoring, and management of these adverse events. Offers a unique and comprehensive publication on the adverse events associated with a new and fast-growing class of medicines Provides a systematic analysis of adverse events aimed at better prevention through understanding and offering insights for the development of safer drugs Uses practical guidelines to establish a leading reference on this class of drugs for educators, researchers, drug developers, clinicians, safety professionals, and more

Major depressive disorders have recently been associated with impairments in signaling pathways that regulate neuroplasticity and cell survival. Agents designed to directly target molecules in these pathways hold promise as new therapeutics for depression. With the collaboration of the most prestigious international specialists in biochemistry, molecular biology, genomics, psychiatry, psychology, and pharmacology, Neurobiology of Depression discusses the nature of the central nervous system circuits responsible for the modifications of neuronal functioning that lead to depression. The book begins by discussing animal, neurophysiological, and neuropsychological models of depression as well as neural foundations. It explores genetic factors that contribute to depression and describes the effect of monoaminergic systems in the central nervous system. Next, the book profiles the rise of psychopharmacology in the treatment of depression and the research into serotonin and monoamine reuptake inhibitors. It examines the role of the glutamatergic, endocannabinoid, and opioid systems in the pathophysiology of mood disorders, as well as the effect of biological rhythms on the human body. Later chapters review the role of CRF-related ligands, CRF receptors, HPA axis activity, and glucocorticoid receptors in the regulation of the stress response and depression. They also describe cytokine modulation of molecular mechanisms. They examine the role of neuropeptide Y, nitric oxide, beta-arrestins, BDNF, and phosphodiesterases, and discuss the use of tachykinin antagonists in treatment. Finally, they analyze the neurobiological basis for the development of new antidepressant agents. Exploring myriad aspects of a disease that plagues a large percentage of the population worldwide, this volume captures the state of the science of this debilitating disorder, facilitating further research and discovery.

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

Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.

First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. The Editorial Board now reflects expertise in the field of hormone action, vitamin action, X-ray crystal structure, physiology, and enzyme mechanisms. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines. This volume focuses on hormones of the limbic system. Longest running series published by Academic Press Contributions by leading international authorities