This book overviews purinergic receptors that are playing key roles in human and pathophysiological processes. The book elaborates on how selective P1 and P2 modulators have been developed as therapeutics for a variety of diseases. It also provides an overview of current perspectives in the design of purinergic receptor modulators and future challenges such as the availability of selective ligands for all receptor subtypes. Divided into 12 chapters, this comprehensive volume also offers a multidisciplinary perspective on the historical evolution, starting with a chapter devoted to the roots and early discoveries of adenosine and its receptors, followed by a twenty-year retrospective on the synthesis, properties, and functional potential of adenosine receptor ligands, probes, and functional conjugates. In the next chapters, experts in the field delve into topics such as the therapeutic potential of adenosine receptor ligands in wound healing and fibrosis, the therapeutic benefits of A2A receptor antagonists, the A2B adenosine receptor as a target for brain ischemia or demyelination, the development and latest advancements in clinical trials of A3 adenosine receptor ligands. Other chapters describe bifunctional tools to study adenosine receptors, allosteric modulators of adenosine receptors, and new computational approaches to inspect adenosine receptor-ligand recognition processes. Furthermore, the book discusses the role of P2X4 receptors in immunity and inflammation. The final chapters illustrate CD73 inhibitors as antitumor agents, and bacterial ectonucleotidases as underexplored antibacterial drug targets. This book is a valuable resource for scholars working in the field of medicinal chemistry, as well as researchers in the industry, providing readers with a comprehensive understanding of adenosine receptor biology and its therapeutic potential.

This book aims to provide a brief update on the functions of purinergic receptors in various systems, in addition to the signaling pathway activated to mediate these functions. We address the influence of hypoxia by modulating the activity of these receptors under physiological and pathophysiological conditions. Additionally, we describe the mechanisms of induction of pain and inflammation in different systems. Finally, the book discusses some of the main bioinformatics tools currently used to improve or discover new prototypes capable of selectively acting on these receptors with estimated parameters of satisfactory solubility and toxicity for possible commercial implementation.

Since their discovery approximately 25 years ago, adenosine receptors have now emerged as important novel molecular targets in disease and drug discovery. These proteins play important roles in the entire spectrum of disease from inflammation to immune suppression. Because of their expression on a number of different cell types and in a number of different organ systems they play important roles in specific diseases, including asthma, rheumatoid arthritis, Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, heart disease, stroke, cancer, sepsis, and obesity. As a result of intense investigations into understanding the molecular structures and pharmacology of these proteins, new molecules have been synthesized that have high specificity for these proteins and are now entering clinical trials. These molecules will define the next new classes of drugs for a number of diseases with unmet medical needs.

This book overviews purinergic receptors that are playing key roles in human and pathophysiological processes. The book elaborates on how selective P1 and P2 modulators have been developed as therapeutics for a variety of diseases. It also provides an overview of current perspectives in the design of purinergic receptor modulators and future challenges such as the availability of selective ligands for all receptor subtypes. Divided into 12 chapters, this comprehensive volume also offers a multidisciplinary perspective on the historical evolution, starting with a chapter devoted to the roots and early discoveries of adenosine and its receptors, followed by a twenty-year retrospective on the synthesis, properties, and functional potential of adenosine receptor ligands, probes, and functional conjugates. In the next chapters, experts in the field delve into topics such as the therapeutic potential of adenosine receptor ligands in wound healing and fibrosis, the therapeutic benefits of A2A receptor antagonists, the A2B adenosine receptor as a target for brain ischemia or demyelination, the development and latest advancements in clinical trials of A3 adenosine receptor ligands. Other chapters describe bifunctional tools to study adenosine receptors, allosteric modulators of adenosine receptors, and new computational approaches to inspect adenosine receptor-ligand recognition processes. Furthermore, the book discusses the role of P2X4 receptors in immunity and inflammation. The final chapters illustrate CD73 inhibitors as antitumor agents, and bacterial ectonucleotidases as underexplored antibacterial drug targets. This book is a valuable resource for scholars working in the field of medicinal chemistry, as well as researchers in the industry, providing readers with a comprehensive understanding of adenosine receptor biology and its therapeutic potential.

This volume aims to cover all major methodological aspects of research into purinergic signaling and to provide a foundation for studying them at molecular, biochemical, pharmacological, and physiological levels. Chapters guide readers through current knock-out and knock-in mouse models, in silico modeling, knock down purinoceptor expression, bioluminiscence resonance energy transfer, enzyme-based biosensors, recording P2X receptor electrophysiology, controlling P2X receptors by optogenetics, inflammasome activation, leukocyte migration, and cell adhesion. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Purinergic Signaling: Methods and Protocols will provide a sound basis for molecular, cellular, and physiological research into purinergic signaling in health and disease and will spark interest in this fascinating signaling process among researchers in many different and unrelated disciplines.

Current Topics in Membranes

An understanding of the nervous system at virtually any level of analysis requires an understanding of its basic building block, the neuron. From Molecules to Networks provides the solid foundation of the morphologic, biochemical, and biophysical properties of nerve cells. All chapters have been thoroughly revised for this second edition to reflect the significant advances of the past 5 years. The new edition expands on the network aspects of cellular neurobiology by adding a new chapter, Information Processing in Neural Networks, and on the relation of cell biological processes to various neurological diseases. The new concluding chapter illustrates how the great strides in understanding the biochemical and biophysical properties of nerve cells have led to fundamental insights into important aspects of neurodegenerative disease. - Written and edited by leading experts in the field, the second edition completely and comprehensively updates all chapters of this unique textbook - Discusses emerging new understanding of non-classical molecules that affect neuronal signaling - Full colour, professional graphics throughout - Includes two new chapters: Information Processing in Neural Networks - describes the principles of operation of neural networks and the key circuit motifs that are common to many networks in the nervous system. Molecular and Cellular Mechanisms of Neurodegenerative Disease - introduces the progress made in the last 20 years in elucidating the cellular and molecular mechanisms underlying brain disorders, including Amyotrophic Lateral Sclerosis (ALS), Parkinson disease, and Alzheimer's disease