Polyamine Metabolism in Disease and Polyamine-Targeted Therapies


Book Description

Polyamines are ubiquitous polycations essential for all cellular life. The most common polyamines in eukaryotes, spermine, spermidine, and putrescine, exist in millimolar intracellular concentrations that are tightly regulated through biosynthesis, catabolism, and transport. Polyamines interact with, and regulate, negatively charged macromolecules, including nucleic acids, proteins, and ion channels. Accordingly, alterations in polyamine metabolism affect cellular proliferation and survival through changes in gene expression and transcription, translation, autophagy, oxidative stress, and apoptosis. Dysregulation of these multifaceted polyamine functions contribute to multiple disease processes, thus their metabolism and function have been targeted for preventive or therapeutic intervention. The correlation between elevated polyamine levels and cancer is well established, and ornithine decarboxylase, the rate-limiting biosynthetic enzyme in the production of putrescine, is a bona fide transcriptional target of the Myc oncogene. Furthermore, induced polyamine catabolism contributes to carcinogenesis that is associated with certain forms of chronic infection and/or inflammation through the production of reactive oxygen species. These and other characteristics specific to cancer cells have led to the development of polyamine-based agents and inhibitors aimed at exploiting the polyamine metabolic pathway for chemotherapeutic and chemopreventive benefit. In addition to cancer, polyamines are involved in the pathologies of neurodegenerative diseases including Alzheimer’s and Parkinson’s, parasitic and infectious diseases, wound healing, ischemia/reperfusion injuries, and certain age-related conditions, as polyamines are known to decrease with age. As in cancer, polyamine-based therapies for these conditions are an area of active investigation. With recent advances in immunotherapy, interest has increased regarding polyamine-associated modulation of immune responses, as well as potential immunoregulation of polyamine metabolism, the results of which could have relevance to multiple disease processes. The goal of this Special Issue of Medical Sciences is to present the most recent advances in polyamine research as it relates to health, disease, and/or therapy.




Polyamine Metabolism in Disease and Polyamine-Targeted Therapies


Book Description

Spermine, spermidine, and putrescine constitute the mammalian polyamines, abundant polycations with essential roles in critical cell functions. As such, intracellular polyamine concentrations are tightly regulated through biosynthesis, catabolism, and transport. The multifaceted effects of polyamine dysregulation have contributed to its role in multiple disease processes but have also implicated it as target for preventive or therapeutic intervention. The correlation between oncogene-mediated elevation of polyamine biosynthesis and cancer is well established, and induced polyamine catabolism contributes to carcinogenesis that is associated with certain forms of chronic infection and/or inflammation. In addition to cancer, polyamines are involved in the pathologies of neurodegenerative diseases, parasitic and infectious diseases, wound healing, ischemia/reperfusion injuries, and certain age-related conditions, as polyamines concentrations are reported to decrease with age. As in cancer, polyamine-based therapies for these conditions are an area of active investigation. With recent advances in immunotherapy, interest has increased regarding polyamine-associated modulation of immune responses as well as potential immunoregulation of polyamine metabolism, the results of which could have relevance to multiple disease processes. The goal of this Special Issue of Medical Sciences is to present the most recent advances in polyamine research as it relates to health, disease, and/or therapy.




Polyamine Cell Signaling


Book Description

Polyamines are organic cations found in all eukaryotic cells and intimately involved in, and required for, distinct biological functions. An increasing body of evidence indicates that the regulation of cellular polyamines is a central convergence point for the multiple signaling pathways driving various cellular functions. Over the last decade, considerable progress has been made in und- standing the molecular functions of cellular polyamines. These significant findings provide a fundamental basis to not only define the exact role of polyamines in physiology, but also to develop new therapeutic approaches for cancers and other diseases. The major objective of this book is to provide a timely and long lasting guide for investigators in the fields of polyamines, physiology, pharmacology, and cancer research. It will provide a foundation based on research and address the potential for subsequent applications in clinical practice. Polyamine Cell Signaling: Physiology, Pharmacology, and Cancer Research is divided into four main parts: Part I: Polyamines in Signal Transduction of Cell Proliferation Part II: Polyamines in Cellular Signaling of Apoptosis, Carcinogenesis, and Cancer Therapy Part III: Polyamines in Cell Motility and Cell–Cell Interactions Part IV: Polyamine Homeostasis and Transport This book not only covers the current state-of-the-art findings relevant to cellular and molecular functions of polyamines, but also provides the underlying conceptual basis and knowledge regarding potential therapeutic targeting of polyamines and polyamine metabolism. These points are addressed by int- nationally recognized experts in their contributions to this book.




Polyamine Drug Discovery


Book Description

This is the first comprehensive description of the discovery and therapeutic potential of polyamine drugs.




Polyamines


Book Description

This book covers key topics in polyamine research from a range of organisms, including plants, mammals, and prokaryotes such as bacteria and archaea. The book provides an introduction to general concepts in the field of polyamine research, as well as more detailed information. With the availability of genome sequence data from a broad range of organisms, the evolution of the genes involved in polyamine metabolism is discussed. The mode of action of polyamines has been shown to be dependent on cation channels, and this mechanism is described in the book. The origin of polyamine transporters (from bacteria, yeasts, and plants) is described. The various effects of polyamines on growth and survival are also documented. The book details the mechanisms of polyamine homeostasis and the role of polyamine molecules as precursors of secondary metabolites such as plant alkaloids and toxins derived from spiders and wasps. The role of polyamines in longevity and disease is discussed. A link between polyamine contents and cancer progression is reported, as is the use of polyamine metabolites as diagnostic markers in the initial stages of cancer. Moreover, a novel approach that utilizes the polyamine pathway of a parasite as a drug target in African sleeping sickness is described. Therefore, this book is a valuable resource, both as a textbook for undergraduate and graduate students and also as a reference book for front-line polyamine researchers.




Inhibition of Polyamine Metabolism


Book Description

Inhibition of polyamine metabolism ...




RSC Drug Discovery, 17


Book Description

Polyamines are ubiquitous molecules that are involved in a number of important cellular processes. Aberrations in their function or metabolism play a role in diseases such as cancer and parasitic infection. A number of validated drug targets have been identified, including enzymes in the polyamine biosynthetic and catabolic pathways and the S-adenosylmethionine synthetic and salvage pathways. Polyamine Drug Discovery is the first comprehensive volume to cover all aspects of the design and development of potential therapeutics targeting polyamine metabolism. The book details research progress f.




Polyamines in Health and Nutrition


Book Description

The importance of polyamines for all living cells has been recognized since spermine was discovered in human semen more than 300 years ago. Polyamine research intensified when analytical methods were developed for their determination, particularly in tissues and biological fluids. Discovering their close correlation with cancer, and that polyamine concentrations change during the cell cycle, gave reason for further research in this topic. Polyamines in Health and Nutrition concentrates on the direction of polyamine research which has the capacity to influence and benefit our health and which can explain some of the discrepancies and failures of earlier research. It is important to recognize the dietary contribution to the polyamine body pool and to investigate how the polyamine content of the diet can be changed, with the ultimate aim of using this information to improve our health.




Polyamines


Book Description

The significance of polyamines in cell proliferation and carcinogenesis has stimulated further research interest in their biochemistry and metabolism. These papers, which update the available literature on polyamines, are grouped into four main areas: the metabolism of polyamines; the effect of polyamines on cellular metabolism; inhibitors of polyamine metabolism and their clinical relevance; application to diagnosis and prognosis. The Proceedings include contributions from a wide range of research interests with special emphasis being placed on the clinical aspects of these compounds.




DNA Methylation and Complex Human Disease


Book Description

DNA Methylation and Complex Human Disease reviews the possibilities of methyl-group-based epigenetic biomarkers of major diseases, tailored epigenetic therapies, and the future uses of high-throughput methylome technologies. This volume includes many pertinent advances in disease-bearing research, including obesity, type II diabetes, schizophrenia, and autoimmunity. DNA methylation is also discussed as a plasma and serum test for non-invasive screening, diagnostic and prognostic tests, as compared to biopsy-driven gene expression analysis, factors which have led to the use of DNA methylation as a potential tool for determining cancer risk, and diagnosis between benign and malignant disease. Therapies are at the heart of this volume and the possibilities of DNA demethylation. In cancer, unlike genetic mutations, DNA methylation and histone modifications are reversible and thus have shown great potential in the race for effective treatments. In addition, the authors present the importance of high-throughput methylome analysis, not only in cancer, but also in non-neoplastic diseases such as rheumatoid arthritis. Discusses breaking biomarker research in major disease families of current health concern and research interest, including obesity, type II diabetes, schizophrenia, and autoimmunity Summarizes advances not only relevant to cancer, but also in non-neoplastic disease, currently an emerging field Describes wholly new concepts, including the linking of metabolic pathways with epigenetics Provides translational researchers with the knowledge of both basic research and clinic applications of DNA methylation in human diseases