Nuclear Receptors As Molecular Targets For Cardiometabolic And Central Nervous System Diseases

Nuclear receptors are a family of transcription factors consisting of 49 members identified in the human genome. Nuclear receptors regulate transcription by binding to response elements in the regulatory regions of target genes and thereby affect expression of genes involved in differentiation, growth, lipid homeostasis, inflammation and immunity. Over the past two decades significant advances have been made in the understanding of the regulation of gene expression by nuclear receptors. The knowledge on nuclear receptors has delivered novel therapies for lipid control and hormone replacement, and for management of cancer and diabetes. Therefore, nuclear receptors are attractive molecular targets for design of therapy for diabetes, obesity, atherosclerosis, cancer, inflammation and neurodegeneration. The focus of this volume is centered on the mechanistic involvement of nuclear receptors in cardiological, metabolic and neurological disorders, on possible explanation of pathways involved in pathogenesis, on susceptibility to and prevention of metabolic and neurological disorders and on the aspects of drug finding including chemistry and rational drug design. This volume reviews recent progress on nuclear receptors critically and will intrigue those pursuing interest in physiology, pathology and medicine.

"Nuclear receptors are a family of transcription factors consisting of 49 members identified in the human genome. Nuclear receptors regulate transcription by binding to response elements in the regulatory regions of target genes and thereby affect expression of genes involved in differentiation, growth, lipid homeostasis, inflammation and immunity. This volume reviews recent progress on nuclear receptors critically and will intrigue those pursuing interest in physiology, pathology and medicine."--BOOK JACKET.

"The ninth Solvay Pharmaceutical Conference on Medicinal Chemistry held in Garmisch-Partenkirchen (Germany) September 26-28, 2007"--P. vi.

Pulmonary hypertension is a fatal lung and heart disease. It is characterized by shortness of breath, fatigue and fainting. It is exacerbated by an increase of the pressure in the lung vasculature through exercise, leading to progressive worsening of hemodynamics, right ventricular hypertrophy, right heart insufficiency and finally right heart failure. This book focuses on pulmonary arterial hypertension, a rare and progressive subgroup of pulmonary hypertension, which is today incurable and terminally faal. Classification of pulmonary arterial hypertension, its pathology, and strategies for future therapy will be of interest both to those suffering from the disease and those who take care of patients. This volume will also engage physicians and other scientists contributing to an understanding of the pathophysiology of pulmonary arterial hypertension and attempting to extend life of humans with pulmonary arterial hypertension by developing causal and curative therapies.

Circadian rhythms, the biological oscillations based around our 24-hour clock, have a profound effect on human physiology and healthy cellular function. Circadian Rhythms: Health and Disease is a wide-ranging foundational text that provides students and researchers with valuable information on the molecular and genetic underpinnings of circadian rhythms and looks at the impacts of disruption in our biological clocks in health and disease. Circadian Rhythms opens with chapters that lay the fundamental groundwork on circadian rhythm biology. Section II looks at the impact of circadian rhythms on major organ systems. Section III then turns its focus to the central nervous system. The book then closes with a look at the role of biological rhythms in aging and neurodegeneration. Written in an accessible and informative style, Circadian Rhythms: Health and Disease,will be an invaluable resource and entry point into this fascinating interdisciplinary field that brings together aspects of neuroscience, cell and molecular biology, and physiology.

Recent years have seen spectacular advances in the field of circadian biology. These have attracted the interest of researchers in many fields, including endocrinology, neurosciences, cancer, and behavior. By integrating a circadian view within the fields of endocrinology and metabolism, researchers will be able to reveal many, yet-unsuspected aspects of how organisms cope with changes in the environment and subsequent control of homeostasis. This field is opening new avenues in our understanding of metabolism and endocrinology. A panel of the most distinguished investigators in the field gathered together to discuss the present state and the future of the field. The editors trust that this volume will be of use to those colleagues who will be picking up the challenge to unravel how the circadian clock can be targeted for the future development of specific pharmacological strategies toward a number of pathologies.

The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References

Edited by two experts working at the pioneering pharmaceutical company and major global player in hormone-derived drugs, this handbook and reference systematically treats the drug development aspects of all human nuclear receptors, including recently characterized receptors such as PPAR, FXR and LXR. Authors from leading pharmaceutical companies around the world present examples and real-life data from their own work.