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Druggable Lipid Signaling Pathways

Druggable Lipid Signaling Pathways
Author: Yasuyuki Kihara
Publisher: Springer Nature
Total Pages: 262
Release: 2020-09-07
Genre: Science
ISBN: 3030506215

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Lipids are responsible not just for constituting cellular membrane but also for storing energy, transducing signaling, and modifying proteins. Bioactive lipids, or lipid mediators, transduce signaling as intracellular messenger like phosphoinoitides, and also regulate cell-cell communication through G protein-coupled receptors (GPCRs) that are potentially valuable drug targets in many diseases. Until now, about 40 GPCRs within ~300 rhodopsin-like (class A) GPCRs, are identified as lipid GPCRs. Advances of lipid research have enabled to develop novel small molecules targeting lipid GPCRs for several diseases. Most notably, fingolimod (FTY720), a sphingosine 1-phosphate (S1P) receptor modulator, became the first FDA-approved medicine as an orally bioavailable drug for treating relapsing forms of multiple sclerosis (MS). In addition to fingolimod, other drugs targeting lipid GPCRs had been developed such as latanoprost (prostaglandin F2a analogue, used for ocular hypertension and glaucoma), epoprostenol and treprostinil (prostaglandin I2 analogue, used for pulmonary arterial hypertension), montelukast and pranlukast (cysteinyl leukotriene receptor antagonist, used for asthma and allergies), etc. Novel drugs are also expected like lysophosphatidic acid (LPA) receptor antagonist for treatment of pulmonary fibrosis. Drug development targeting lipid signalling pathways are backdated to more than a century, when aspirin was synthesized and selling by Bayer, while the basic mechanism of aspirin's effects (block prostanoid synthesis by inhibiting cyclooxygenases) had not been discovered until 1970s. Nowadays, non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprophen are commonly used as antipyretic analgesics and available readily over-the-counter oral drugs. Both upstream and downstream enzymes, such as phospholipase A2s and prostaglandin E synthases, respectively, are also potential therapeutic targets for inflammatory diseases. Recent studies of lipid metabolism expand the lipid biology field from pro-inflammatory lipid mediators to anti-inflammatory epoxy fatty acids (epoxyeicosatrienoic acids), and also omega-3 fatty acid-derived pro-resolving lipid mediators (lipoxin, resolvin, and neuroprotectin). These bioactive lipids, their metabolic pathways and receptors are of great interest in developing next-generation anti-inflammatory and pro-resolving drugs for a wide variety of diseases including. This book summarizes not only historical overview of lipid signaling pathways but also provides summary of cutting-edge studies that may provide some hints of novel “druggable” lipid signaling targets.


Structural Biology in Drug Discovery

Structural Biology in Drug Discovery
Author: Jean-Paul Renaud
Publisher: John Wiley & Sons
Total Pages: 706
Release: 2020-02-05
Genre: Medical
ISBN: 1118681010

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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


Handbook of Molecular Biotechnology

Handbook of Molecular Biotechnology
Author: Dongyou Liu
Publisher: CRC Press
Total Pages: 763
Release: 2024-09-05
Genre: Science
ISBN: 1040005640

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With a history that likely dates back to the dawn of human civilization more than 10,000 years ago, and a record that includes the domestication and selective breeding of plants and animals, the harnessing of fermentation process for bread, cheese, and brewage production, and the development of vaccines against infectious diseases, biotechnology has acquired a molecular focus during the 20th century, particularly following the resolution of DNA double helix in 1953, and the publication of DNA cloning protocol in 1973, and transformed our concepts and practices in disease diagnosis, treatment and prevention, pharmaceutical and industrial manufacturing, animal and plant industry, and food processing. While molecular biotechnology offers unlimited opportunities for improving human health and well-being, animal welfare, agricultural innovation and environmental conservation, a dearth of high quality books that have the clarity of laboratory manuals without distractive procedural details and the thoroughness of well-conversed textbooks appears to dampen the enthusiasm of aspiring students. In attempt to fill this glaring gap, Handbook of Molecular Biotechnology includes four sections, with the first three presenting in-depth coverage on DNA, RNA and protein technologies, and the fourth highlighting their utility in biotechnology. Recognizing the importance of logical reasoning and experimental verification over direct observation and simple description in biotechnological research and development, the Introduction provides pertinent discussions on key strategies (i.e., be first, be better, and be different), effective thinking (lateral, parallel, causal, reverse, and random), and experimental execution, which have proven invaluable in helping advance research projects, evaluate and prepare research reports, and enhance other scientific endeavors. Key features Presents state-of-the-art reviews on DNA, RNA and protein technologies and their biotechnological applications Discusses key strategies, effective thinking, and experimental execution for scientific research and development Fills the gap left by detailed-ridden laboratory manuals and insight-lacking standard textbooks Includes expert contributions from international scientists at the forefront of molecular biotechnology research and development Written by international scientists at the forefront of molecular biotechnology research and development, chapters in this volume cover the histories, principles, and applications of individual techniques/technologies, and constitute stand-alone, yet interlinked lectures that strive to educate as well as to entertain. Besides providing an informative textbook for tertiary students in molecular biotechnology and related fields, this volume serves as an indispensable roadmap for novice scientists in their efforts to acquire innovative skills and establish solid track records in molecular biotechnology, and offers a contemporary reference for scholars, educators, and policymakers wishing to keep in touch with recent developments in molecular biotechnology.


Nuclear G-Protein Coupled Receptors

Nuclear G-Protein Coupled Receptors
Author: Bruce G. Allen
Publisher: Humana
Total Pages: 0
Release: 2016-08-23
Genre: Science
ISBN: 9781493955466

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Nuclear G-Protein Coupled Receptors: Methods and Protocols is a compilation of a number of conceptual and methodological aspects important for the validation and characterization of intacrine signaling systems. To date, the best-characterized intracrine signaling system is that of angiotensin II (Ang II), covered in depth in various chapters. Methodology to study the subcellular localization and function of GPCRs and other signaling systems is provided, as well as numerous chapters focusing on methods designed to understand signaling mediated by nuclear and other internal GPCRs. Methods are also described to study the formation of second messengers such as cAMP and to study the trafficking of receptors from the cell surface. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Nuclear G-Protein Coupled Receptors: Methods and Protocols seeks to serve both professionals and novices with state-of-the-art approaches to characterize what is becoming a common theme in cellular signaling.


Fiber Pathways of the Brain

Fiber Pathways of the Brain
Author: Jeremy D. Schmahmann
Publisher: OUP USA
Total Pages: 674
Release: 2009-02-11
Genre: Medical
ISBN: 0195388267

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The text is enriched throughout by close attention to functional aspects of the anatomical observations."--Jacket.


Cellular Mechanotransduction

Cellular Mechanotransduction
Author: Mohammad R. K. Mofrad
Publisher: Cambridge University Press
Total Pages: 0
Release: 2014-07-31
Genre: Technology & Engineering
ISBN: 9781107682467

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"Mechanotransduction" is the term for the ability, first described by 19th-century anatomist Julius Wolff, of living tissues to sense mechanical stress and respond by tissue remodeling. More recently, the scope of mechanotransduction has been expanded to include the sensation of stress, its translation into a biochemical signal, and the sequence of biological responses it produces. This book looks at mechanotransduction in a more restricted sense, focusing on the process of stress sensing and transducing a mechanical force into a cascade of biochemical signals. This stress has become increasingly recognized as one of the primary and essential factors controlling biological functions, ultimately affecting the function of the cells, tissues, and organs. A primary goal of this broad book is also to help define the new field of mechanomics, which attempts to describe the complete mechanical state of a biological system.


Kisspeptin Signaling in Reproductive Biology

Kisspeptin Signaling in Reproductive Biology
Author: Alexander S. Kauffman
Publisher: Springer Science & Business Media
Total Pages: 515
Release: 2013-04-02
Genre: Medical
ISBN: 1461461995

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Kisspeptin has been shown to be both necessary and sufficient for activation of the reproductive axis, during puberty and later in adulthood. This makes kisspeptin a fundamental component of the reproductive axis. Kisspeptin has been deemed the single most potent stimulator of GnRH neurons yet known. The importance of kisspeptin has been documented in humans as well as non-human animal models, ranging from monkeys, sheep, and rodents to numerous fish species, thus signifying a highly conserved nature of its reproductive function. Importantly, kisspeptin neurons seem to mediate many of the regulatory effects of other signals, whether they are metabolic, circadian, hormonal, or stress. This places kisspeptin neurons in a unique position to be key nodal points and conduits for conveying numerous endogenous and exogenous signals to the reproductive axis.


Fundamentals of Protein NMR Spectroscopy

Fundamentals of Protein NMR Spectroscopy
Author: Gordon S. Rule
Publisher: Springer Science & Business Media
Total Pages: 543
Release: 2006-02-16
Genre: Science
ISBN: 1402035004

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NMR spectroscopy has proven to be a powerful technique to study the structure and dynamics of biological macromolecules. Fundamentals of Protein NMR Spectroscopy is a comprehensive textbook that guides the reader from a basic understanding of the phenomenological properties of magnetic resonance to the application and interpretation of modern multi-dimensional NMR experiments on 15N/13C-labeled proteins. Beginning with elementary quantum mechanics, a set of practical rules is presented and used to describe many commonly employed multi-dimensional, multi-nuclear NMR pulse sequences. A modular analysis of NMR pulse sequence building blocks also provides a basis for understanding and developing novel pulse programs. This text not only covers topics from chemical shift assignment to protein structure refinement, as well as the analysis of protein dynamics and chemical kinetics, but also provides a practical guide to many aspects of modern spectrometer hardware, sample preparation, experimental set-up, and data processing. End of chapter exercises are included to emphasize important concepts. Fundamentals of Protein NMR Spectroscopy not only offer students a systematic, in-depth, understanding of modern NMR spectroscopy and its application to biomolecular systems, but will also be a useful reference for the experienced investigator.