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Introductory Review on Sirtuins in Biology and Disease provides key insights for scientists and advanced students who need to understand sirtuins and the current research in this field. This book is ideal for pharmaceutical companies as they develop novel targets using sirtuins for metabolic diseases, cancer and neurodegenerative illnesses. Sirtuins are a diverse family of proteins, with several members in mammals. The functional diversity of sirtuins is rather broad, and they have been implicated in various central biological processes. Thus, they are also highly relevant in the context of various human diseases, from cancer to neurodegeneration. - Covers both the general and specific aspects of sirtuin proteins and their role in biology, aging and disease - Presents a top quality collection of leading experts who contribute on a wide range of sirtuin-related topics - Ideal resource for pharmaceutical companies as they develop novel targets using sirtuins for metabolic diseases, cancer and neurodegenerative illnesses
Sirtuin Biology in Cancer and Metabolic Disease: Cellular Pathways for Clinical Discovery offers a compelling and thought-provoking perspective for the examination of the intriguing biology of sirtuins that ties cancer and metabolic disease together and provides a critical platform for the development of sirtuin-based novel therapeutic strategies to effectively treat cancer and metabolic disorders with precision in order to minimize any potentially detrimental clinical outcomes. An exciting prospect for the development of innovative therapeutics for cancer and metabolic disorders involves sirtuins. Sirtuins are histone deacetylases that have an intricate role in the onset and development of cancer and metabolic disease. Implementing a translational medicine format, this innovative reference highlights the ability of sirtuins to oversee critical pathways that involve stem cell maintenance, cellular proliferation, metabolic homeostasis, apoptosis, and autophagy that can impact cellular dysfunction and unchecked cellular growth that can occur during cancer and metabolic disease. Each chapter offers an intuitive perspective of advances on the application of sirtuin pathways for cancer and metabolic disease that will be become a "go-to" resource for a broad audience of scientists, physicians, pharmaceutical industry experts, nutritionists, and students. - Chapters are authored by internationally recognized experts who elucidate the intimate relationship between cancer and metabolic disease that intersects with sirtuin pathways - Presents the basic and clinical role of sirtuins in regard to cancer and metabolic disease - Summarizes the multidiscipline views and publications for this exciting field of sirtuins for the development of new clinical treatments for cancer and metabolic disease - Provides a vital foundation for a broad audience of healthcare providers, scientists, drug developers, and students in both clinical and research settings
Sirtuins comprise a family of NAD+-dependent enzymes that have been shown to impact longevity in a number of eukaryotic organisms. Sir2 (Silent Information Regulator 2) was the first sirtuin protein discovered. The discovery that Sir2 requires NAD+ for its activity suggested a link between Sir2 activity and the phenomenon of caloric restriction in prolonging longevity. This link was strengthened by the observation that lifespan extension by caloric restriction requires Sir2 protein. Under conditions of caloric restriction, NAD+ levels are high, Sir2 is activated, and the rate of aging is decreased. These effects have been replicated in invertebrate organisms, where a close structural and functional homologue of Sir2 was found in C. elegans and Drosophila. The sirtuin-dependent effects on metabolism and ageing, observed in lower organisms, have ignited intensive investigation of their biological and therapeutic roles in mammals. There are seven known mammalian sirtuins, SIRTs 1-7, the most studied of which is SIRT1, a close structural and functional homologue of yeast Sir2. Enhancement of organismal longevity and other health-promoting effects of mammalian SIRT1 have frequently been attributed to the regulation of metabolism. A recognized molecular link between metabolism and aging stimulated a firestorm of investigations, aiming to combat metabolic and age-dependent human diseases. It has become clear, however, that the sirtuin family of proteins regulates a diverse repertoire of cellular functions in mammals. Mounting evidence implicating SIRT1 in important clinical indications, such as diabetes, cancer, cardiovascular dysfunction and neurodegenerative disease, suggest that modality as attractive therapeutic target. Subsequently, drug discovery and development, targeting sirtuin activation, has been intensified in the recent years. Despite rapid progress and accumulation of new data, the biological roles of other mammalian sirtuins have been less studied and remain poorly understood. There are several important questions that remain to be addressed. What are the functions of sirtuins in different cell types and tissues? Are all sirtuins involved in the regulation of metabolism and aging? What is the functional relationship between different sirtuins? What are the mechanisms of regulation of sirtuin activities? What is the role of sirtuins in disease and therapy? This issue aims to address these and other critical questions, relevant to Research Topic on sirtuin biology and therapeutics. To that end the issue solicits expert opinions of sirtuin research on structural biology, biochemistry, cell biology, animal genetics, pharmacology, medicinal chemistry and drug discovery, and on areas of investigation studying human conditions, like diabetes, cancer, cardio-vascular, and neutodegeneration. Of particular interest are the new methods and assays to study sirtuins in various organisms and developing sirtuin-based therapeutics. Furthermore, we propose to encourage contributors to discuss new concepts and paradigms, and to express their perspectives on the future development of the sirtuin research field. Altogether, we believe this issue provides a unique opportunity for comprehensive and diverse coverage of the topic, and will be of broad interest for the journal’s readership.
Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
The book highlights work from many different labs that taught us abnormal HDACs potentially contribute to the development or progression of many human diseases including immune dysfunctions, heart disease, cancer, memory impairment, aging, and metabolic disorders.
Sirtuin Biology in Cancer and Metabolic Disease: Cellular Pathways for Clinical Discovery offers a compelling and thought-provoking perspective for the examination of the intriguing biology of sirtuins that ties cancer and metabolic disease together and provides a critical platform for the development of sirtuin-based novel therapeutic strategies to effectively treat cancer and metabolic disorders with precision in order to minimize any potentially detrimental clinical outcomes. An exciting prospect for the development of innovative therapeutics for cancer and metabolic disorders involves sirtuins. Sirtuins are histone deacetylases that have an intricate role in the onset and development of cancer and metabolic disease. Implementing a translational medicine format, this innovative reference highlights the ability of sirtuins to oversee critical pathways that involve stem cell maintenance, cellular proliferation, metabolic homeostasis, apoptosis, and autophagy that can impact cellular dysfunction and unchecked cellular growth that can occur during cancer and metabolic disease. Each chapter offers an intuitive perspective of advances on the application of sirtuin pathways for cancer and metabolic disease that will be become a "go-to" resource for a broad audience of scientists, physicians, pharmaceutical industry experts, nutritionists, and students. Chapters are authored by internationally recognized experts who elucidate the intimate relationship between cancer and metabolic disease that intersects with sirtuin pathways Presents the basic and clinical role of sirtuins in regard to cancer and metabolic disease Summarizes the multidiscipline views and publications for this exciting field of sirtuins for the development of new clinical treatments for cancer and metabolic disease Provides a vital foundation for a broad audience of healthcare providers, scientists, drug developers, and students in both clinical and research settings
Nearly a century of scientific research has revealed that mitochondrial dysfunction is one of the most common and consistent phenotypes of cancer cells. A number of notable differences in the mitochondria of normal and cancer cells have been described. These include differences in mitochondrial metabolic activity, molecular composition of mitochondria and mtDNA sequence, as well as in alteration of nuclear genes encoding mitochondrial proteins. This book, Mitochondria and Cancer, edited by Keshav K. Singh and Leslie C. Costello, presents thorough analyses of mitochondrial dysfunction as one of the hallmarks of cancer, discusses the clinical implications of mitochondrial defects in cancer, and as unique cellular targets for novel and selective anti-cancer therapy.
This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease
This multivolume reference work addresses the fact that the well being of humankind is predicated not only on individuals receiving adequate nutrition but also on their genetic makeup. The work includes more than 100 chapters organized in the following major sections: Introduction and Overview; Epigenetics of Organs and Diseases in Relation to Diet and Nutrition; Detailed Processes in Epigenetics of Diet and Nutrition; Modulating Epigenetics with Diet and Nutrition; and Practical Techniques. While it is well known that genes may encode proteins responsible for structural and dynamic components, there is an increasing body of evidence to suggest that nutrition itself may alter the way in which genes are expressed via the process of epigenetics. This is where chemically imposed alteration in the DNA sequence occurs or where the functional expression of DNA is modulated. This may include changes in DNA methylation, non-coding RNA, chromatin, histone acetylation or methylation, and genomic imprinting. Knowledge regarding the number of dietary components that impact on epigenetic processes is increasing almost daily. Marshalling all the information on the complex relationships between diet, nutrition, and epigenetic processes is somewhat difficult due to the wide myriad of material. It is for this reason that the present work has been compiled.
With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins