Nuclear Receptors: From Structure to the Clinic

Nuclear Receptors: From Structure to the Clinic PDF

Author: Iain J. McEwan

Publisher: Springer

Published: 2015-08-20

Total Pages: 236

ISBN-13: 3319187295

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Nuclear Receptors focuses on the structural analysis of nuclear receptors from the initial work using isolated protein domains to the more recent exciting developments investigating the conformational shape of full-length receptor complexes. The book also reviews the structure of key nuclear receptor co-regulatory proteins. It brings together, for the first time, a comprehensive review of nuclear receptor structure and the importance of receptor conformation underpinning allosteric regulation by different ligands (hormone, drugs, DNA response elements, protein-protein interactions) and receptor activity. The nuclear receptor superfamily, including receptors for steroid hormones and non-steroid ligands, are pivotal to normal physiology, regulating processes as diverse as reproduction, metabolism, the immune system and brain development. The first members of the family were cloned over 25 years ago, which heralded in the idea of a superfamily of intracellular receptor proteins that bound small molecule ligands: classical steroid hormones, vitamins, fatty acids and other products of metabolism. These signals are then transmitted through multiprotein receptor-DNA complexes, leading to the regulation of target genes, often in a cell-selective manner. The cloning of the receptor cDNAs also ushered in an era of unparalleled analysis of the mechanisms of action of these ligand-activated transcription factors. ​

Metabolism and Disease

Metabolism and Disease PDF

Author: Terri Grodzicker

Publisher:

Published: 2011

Total Pages: 0

ISBN-13: 9781936113569

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"The Symposium aimed to integrate a very broad field of investigative effort, bringing together advances in our understanding of energy intake, consumption, and storage (diet, exercise, and fat), oxygen regulation and hypoxia, circadian rhythms, and life span/aging. The Symposium explored metabolism at molecular (gene expression, posttranslational modifications, protein turnover, cofactors and integrators, hormones, and signals), organellar (mitochondria), cellular, organ system (cardiovascular, bone), and organismal (timing and life span) scales. Diseases impacted by metabolic imbalance or dysregulation that were covered in detail included diabetes, obesity, metabolic syndrome, and cancer. New and emerging technologies were presented for simultaneous monitoring of hundreds of metabolites that allow for sophisticated sampling of the metabolic state of cells. Because the Symposium covered such a broad field, by necessity much excellent work could not be included, and instead, the Proceedings should be viewed as a necessarily eclectic collection of some of the most interesting and stimulating work that came to the organizers' attention during the 18 months before the meeting"--Page XV.

Nuclear Hormone Receptors

Nuclear Hormone Receptors PDF

Author: Malcolm G. Parker

Publisher:

Published: 1991

Total Pages: 434

ISBN-13:

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An overview of the supergene family made up of those nuclear hormone receptors which recognize thyroid and steroid hormones, vitamen D and retinoic acid and which are characterized by their ability to bind both ligands and the genes which respond to them.

Nuclear Receptors as Drug Targets

Nuclear Receptors as Drug Targets PDF

Author: Eckhard Ottow

Publisher: John Wiley & Sons

Published: 2008-09-08

Total Pages: 522

ISBN-13: 3527623302

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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.

Computational Approaches to Nuclear Receptors

Computational Approaches to Nuclear Receptors PDF

Author: Pietro Cozzini

Publisher: Royal Society of Chemistry

Published: 2012-11-30

Total Pages: 191

ISBN-13: 1849735352

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Nuclear receptors (NR) are ligand-induced activated transcription factors that are involved in numerous biological processes. Since the 1990's when the first structures were determined by means of X ray diffraction, the number of NR structures has increased considerably. Moreover several 'omics' projects (genomics, pharmcogenomics and proteomics) have opened up great opportunities for the discovery of new targets, the characterization of abnormal protein patterns, the selection of "tailored" drugs and the evaluation of drug efficacy even with a lack of structural data. Furthermore, structure-based drug design, computational methods for in silico screening and nanobiotechnology- based tools are simplifying this time-consuming and money-intensive research of lead compounds and, possibly, new drugs. Biological interactions such as those that occur between a protein and ligand are concerted events where flexible molecules interact. Thus understanding flexibility of large molecules or biological complexes is of primary importance to help define the right model to approximate the reality for drug discovery, virtual screening, food safety analysis, etc. NRs are known as flexible targets, with many structural similarities, in particular for their Ligand Binding Domain: these similarities could be assumed to share behavioural qualities that belong to this class of compounds. Thus to supply a possible, complete and exhaustive answer to questions about the behaviour of NRs, their interactions with new potential drugs, endocrine disruptors such as animal and human food toxins, food additives or industry residuals, it is mandatory to approach the problem from a different point of view: a molecular modelling approach, steered synthesis, and in vitro and in vivo tests, etc. The aim of this book is to provide a state of the art review on investigations into Nuclear Receptors.

Steroid Hormone Action

Steroid Hormone Action PDF

Author: Malcolm G. Parker

Publisher: IRL Press

Published: 1993

Total Pages: 242

ISBN-13:

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This volume provides a detailed overview of the mechanisms by which steroid hormones regulate gene activity in target cells. It should be of interest to molecular biologists, endocrinologists, pharmacologists and clinicians interested in gene regulation hormones and steroid antagonists.

Nuclear Receptors

Nuclear Receptors PDF

Author: Mostafa Z. Badr

Publisher: Springer Nature

Published: 2021-09-28

Total Pages: 676

ISBN-13: 3030783154

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Nuclear receptors are ligand activated transcription factors that control numerous biological functions. Consequently, altering activity of these receptors is proposed, and indeed documented, to affect many physiological and pathological conditions in experimental animals and humans. Thus, nuclear receptors have become a major target in the effort to treat numerous diseases. This book will shed light on and emphasize intricate processes involved in designing as well as discovering physiological and pharmacological modulators of these important proteins. World-renowned scientists will share with the reader their professional expertise and extensive experience acquired through decades working with nuclear receptors. Chapters address the various means and consequences of modulating nuclear receptor activity will be presented and discussed. These modulators cover a wide span of moieties ranging from synthetic chemicals to natural products. In addition, the classification of these chemicals ranges from pan agonists to selective agonists and inverse agonists to antagonists. They also include proteolytic means to obliterate the receptor in the event that modulating its activity through canonical pharmacological agents becomes less effective and/or less desirable due to anticipated or experienced toxicities. Modulation of receptor activity may also take place in the absence of a ligand or through manipulating the structure of the receptor itself by controlling posttranslational events.

The Nuclear Receptor Superfamily

The Nuclear Receptor Superfamily PDF

Author: Iain J. McEwan, PhD

Publisher: Humana Press

Published: 2008-12-12

Total Pages: 0

ISBN-13: 9781603275743

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Acting principally to control patterns of gene expression, nuclear receptors play vital roles during embryonic development and in the regulation of metabolic and reproductive functions in adult life, which proves this superfamily of ligand-activated transcription factors to be a crucial part of biological life. In The Nuclear Receptor Superfamily: Methods and Protocols, expert researchers describe a range of molecular, structural and cell biological techniques currently used to investigate the structure-function of nuclear receptors, together with experimental approaches that may lead to new therapeutic strategies for treating nuclear receptor-associated diseases. Written in the highly successful Methods in Molecular BiologyTM series format, the chapters in this volume contain brief introductions to the topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, as well as notes from the experts to highlight tips on troubleshooting and avoiding known pitfalls. Cutting-edge and easy to use, The Nuclear Receptor Superfamily: Methods and Protocols provides beneficial and time-saving guidance for all those undertaking research in this ever-growing field of study.

Prostate Cancer

Prostate Cancer PDF

Author: Scott M. Dehm

Publisher: Springer Nature

Published: 2020-01-03

Total Pages: 483

ISBN-13: 303032656X

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The purpose of this book is to provide a contemporary overview of the causes and consequences of prostate cancer from a cellular and genetic perspective. Written by experts in the fields of epidemiology, toxicology, cell biology, genetics, genomics, cell-cell interactions, cell signaling, hormone signaling, and transcriptional regulation, the text covers aspects of prostate cancer from disease initiation to metastasis. Chapters explore in depth the cells of origin for prostate cancer, its genomic subtypes, neural transcription factors in disease progression, epigenetic regulation of chromatin, and many other topics. This book distinguishes itself from other texts on prostate cancer by its focus on cellular and genetic mechanisms, as opposed to clinical diagnosis and management. As a result, this book will be of broad interest to basic and translational scientists with familiarity of these topics, as well as to trainees at earlier stages of their research careers.