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HSPs - Ambiguous Mediators of Immunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451524 Year: Pages: 92 DOI: 10.3389/978-2-88945-152-4 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2017-08-28 14:01:09
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Heat shock proteins (HSPs) were discovered as polypeptides induced by stress that can be found in all kingdoms of cellular organisms. Their functions were, a first enigmatic and these proteins were thus classified by molecular weight, as in—Hsp27, Hsp70, Hsp90, Hsp110. More recently, each of these size-classified molecules has attributed a role in protein folding, and they thus came to be known, as a class, as molecular chaperones. However, the they possess properties beyond chaperoning. Indeed, their discovery in the extracellular spaces suggested roles in regulation of the immune responses.

ATP-gated P2X receptors in Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194056 Year: Pages: 172 DOI: 10.3389/978-2-88919-405-6 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Extracellular ATP is currently recognized as one of the most widely distributed neurotransmitters and neuromodulators in the peripheral and central nervous system. ATP-gated P2X receptors are expressed by neurons, glial and many other non-neuronal cells and represent an attractive target for therapeutic interventions. Diverse molecular and cellular mechanisms have been identified for P2X receptor functioning, including the ability to enlarge the size of the ion pore associated with the release of several key immune molecules. A major recent breakthrough was the determination of the X-ray crystal structures of zebrafish P2X4 receptor in ATP-bound and ATP-free states. The P2X receptor research field is rapidly growing, as evidenced by the almost 2000 papers published in the last 5 years. However, despite the fundamental signalling function of extracellular ATP in the nervous system, the widespread roles of P2X receptors have not been widely elucidated and presented in textbooks. In this volume of papers we aim to gather a collection of high quality papers, detailing the latest insights from the most accomplished international P2X receptor researchers. Importantly, basic research into P2X receptors has a strong translational impact and our collection of articles could be a valuable guide for the development of new pharmacological and biotechnological tools addressing the function of P2X receptors. Within this collection we plan to cover receptor structure-function relationships, receptors trafficking, to highlight the special properties of P2X receptors and their pharmacological profiles, and to describe the translational aspects of cellular ATP signaling in pain and in other neurological and vascular diseases.

Social Hormones and Human Behavior: What Do We Know and Where Do We Go from Here

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194070 Year: Pages: 95 DOI: 10.3389/978-2-88919-407-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Oxytocin (OT) and arginine vasopressin (AVP) are the paramount social hormones in mammals and accumulating evidence also strengthens the unique role of these neuropeptides also in human social behavior. Indeed from voles to humans, OT and AVP modulate an intriguing number of social behaviors resonating across species such as the quality of pair bonding, parenting, modulations of social stress, in-group & out-group relationships and social communications. Recent molecular genetic studies of the oxytocin (OXTR), arginine vasopressin 1a (AVPR1a) and arginine vasopressin 1b (AVPR1b) receptors have strengthened the role of these two neuropeptides in a range of normal and pathological human behaviors. Importantly, dysfunctions in the OT and AVP neural pathways are likely contributing to deficits in social skills and communication in disorders such as autism. This Research Topic covers the state of the science and provides a deep view of social hormone research in humans to illustrates how pharmacological, genetic and neuroimaging strategies can be successfully combined toward unraveling the mystery of how human social behavior is regulated. Understanding human social behavior at the molecular level, i.e. social neuroscience, is not only crucial for treatment and diagnosis of disorders characterized by deficits in social cognition but also has important implications in establishing the congruence of findings from different approaches in the Social Sciences and Biology. We bring together in this issue a broad spectrum of investigators from the neurosciences, genetics, psychology, economics and political science towards a deeper understanding of the biological roots of human social behavior. We hope that this transdisciplinary Research Topic will bring new insights and ideas to the field, give future perspectives while also addressing open questions and limitation in order to develop intervention and prevention strategies, and to translate the basic social hormone research into clinical applications. This Research Topic covers the state of the science and provides a deep view of social hormone research in humans to illustrates how pharmacological, genetic and neuroimaging strategies can be successfully combined toward unraveling the mystery of how human social behavior is regulated. Understanding human social behavior at the molecular level, aka social neuroscience, is not only crucial for treatment and diagnosis of disorders characterized by deficits in social cognition but such an understanding has important implications for consilience of the Social Sciences and Biology. We bring together in this issue a broad spectrum of investigators from the neurosciences, genetics, psychology, economics and political science towards a deeper understanding of the biological roots of human social behavior. We hope that this transdisciplinary Research Topic will bring new insights and ideas to the field, give future perspectives while also addressing open questions and limitation in order to develop intervention and prevention strategies, and to translate the basic social hormone research into clinical applications.

Insomnia and beyond - Exploring the therapeutic potential of orexin receptor antagonists

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193301 Year: Pages: 219 DOI: 10.3389/978-2-88919-330-1 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Therapeutics --- Neurology --- Medicine (General) --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Orexin/hypocretin neuropeptides, produced by a few thousand neurons in the lateral hypothalamus, are of critical importance for the control of vigilance and arousal of vertebrates, from fish to amphibians, birds and mammals. Two orexin peptides, called orexin-A and orexin-B, exist in mammals. They bind with different affinities to two distinct, widely distributed, excitatory G-protein- coupled receptors, orexin receptor type 1 and type 2 (OXR-1/2). The discovery of an OXR mutation causing canine narcolepsy, the narcolepsy-like phenotype of orexin peptide knockout mice, and the orexin neuron loss associated with human narcoleptic patients laid the foundation for the discovery of small molecule OXR antagonists as novel treatments for sleep disorders. Proof of concept studies from Glaxo Smith Kline, Actelion Pharmaceuticals Ltd. and Merck have now consistently demonstrated the efficacy of dual OXR antagonists (DORAs) in promoting sleep in rodents, dogs, non-human primates and humans. Some of these antagonists have completed late stage clinical testing in primary insomnia. Orexin drug discovery programs have also been initiated by other large pharmaceutical companies including Hoffmann La Roche, Novartis, Eli Lilly and Johnson & Johnson. Orexins are increasingly recognized for orchestrating the activity of the organism’s arousal system with appetite, reward and stress processing pathways. Therefore, in addition to models of insomnia, pharmacological effects of DORAs have begun to be investigated in rodent models of addiction, depression and anxiety. The first clinical trials in diabetic neuropathy, migraine and depression have been initiated with Merck’s MK-6096 (www.clinicaltrials.gov). Whereas the pharmacology of DORAs is established for their effects on wakefulness, pharmacological effects of selective OXR-1 or OXR-2 antagonists (SORAs) have remained less clear. From an evolutionary point of view, the OXR-2 was expressed first in most vertebrate lineages, whereas the OXR-1 is believed to result from a gene duplication event, when mammals emerged. Yet, both receptors do not have redundant function. Their brain expression pattern, their intracellular signaling, as well as their affinity for orexin-A and orexin-B differs. During the past decade most preclinical research on selective OXR-1 antagonism was performed with SB-334867. Only in recent years, other selective OXR-1 and OXR-2 antagonists with optimized selectivity profiles and pharmacokinetic properties have been discovered, and phenotypes of OXR-1 and OXR-2 knockout mice were described. The present Research Topic (referred to in the Editorial as “special topics issue”) comprises submissions of original research manuscripts as well as reviews, directed towards the neuropharmacology of OXR antagonists. The submissions are preclinical papers dealing with dual and/or selective OXR antagonists that shed light on the differential contribution of endogenous orexin signaling through both OXRs for cellular, physiological and behavioral processes. Some manuscripts also report on convergence or divergence of DORA vs. SORA effects with phenotypes expressed by OXR-1 or OXR-2 knockout animals. Ultimately these findings may help further define the potential of DORAs and SORAs in particular therapeutic areas in insomnia and beyond insomnia.

Genome-wide view on the physiology of vitamin D

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193493 Year: Pages: 194 DOI: 10.3389/978-2-88919-349-3 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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The main physiological actions of the biologically most active metabolite of vitamin D, 1a,25-dihydroxyvitamin D3(1a,25(OH)2D3), are calcium and phosphorus uptake and transport and thereby controlling bone formation. Other emergent areas of 1a,25(OH)2D3 action are in the control of immune functions, cellular growth and differentiation. This fits both with the widespread expression of the VDR and the above described consequences of vitamin D deficiency. Transcriptome-wide analysis indicated that per cell type between 200 and 600 genes are primary targets of vitamin D. Since most of these genes respond to vitamin D in a cell-specific fashion, the total number of vitamin D targets in the human genome is far higher than 1,000. This is supported by the genome-wide view on VDR binding sites in human lymphocytes, monocytes, colon and hepatic cells. All genomic actions of 1a,25(OH)2D3 are mediated by the transcription factor vitamin D receptor (VDR) that has been the subject of intense study since the 1980’s. Thus, vitamin D signaling primarily implies the molecular actions of the VDR. In this research topic, we present in 15 chapters different perspectives on the action of vitamin D and its receptor, such as the impact of the genomewide distribution of VDR binding loci, ii) the transcriptome- and proteome-wide effects of vitamin D, iii) the role of vitamin D in health, iv) tissue-specific functions of vitamin D and v) the involvement of vitamin D in different diseases, such as infections, autoimmune diseases, diabetes and different types of cancer.

Thyroid hormone in brain and brain cells

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197026 Year: Pages: 106 DOI: 10.3389/978-2-88919-702-6 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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Thyroid hormone signaling has been known for a long time to be required for proper neurodevelopment and the maintenance of cognitive functions in the adult brain. As thyroid hormone excess or deficiency is usually well handled by clinicians, research dedicated to the neural function of thyroid hormone, have not been a priority within the field. This is changing mainly for two reasons. First, new genetic diseases have been discovered, altering thyroid hormone signaling in brain (THRA, MCT8, SBP2), with neurodevelopmental consequences which are currently incurable. Second, there is a growing concern that exposition of the general population to environmental chemicals able to interfere with thyroid hormone signaling compromises children neurodevelopment or induces central disorders in adults. Finally thyroid hormone is acting directly on gene transcription, by binding nuclear receptors, and therefore is an interesting entry point to identify genetic programs controlling brain development and function. Reaching a broad understanding of the multiple processes involving thyroid hormone in brain is a tremendous task which will necessitate a multidisciplinary approach: animal genetics, molecular biology, brain imaging, developmental biology, genomics, etc... This topic will be the occasion to combine recent contributions in the field and to identify priorities for future investigations. Due to devastating consequences of congenital hypothyroidism, the neurodevelopmental consequences of altered thyroid hormone signaling have been extensively studied over the years. The discovery of new genetic diseases, the concern about the possible neurotoxicity of environmental thyroid hormone disruptors, recently renewed the interest for an important research field. This Ebook gathers reviews and original data from experts in various disciplines. It provides a broad view of ongoing research and outlines key issues for future investigation.

Enterotoxins: Microbial Proteins and Host Cell Dysregulation

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ISBN: 9783038421634 9783038421641 Year: Pages: 306 DOI: 10.3390/books978-3-03842-164-1 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2016-06-03 11:14:38
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Chimica farmaceutica: farmaci sistemici: Lezioni del prof. Ettore Novellino

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Book Series: Phármakon ISBN: 9788868870157 Year: Volume: 1 Pages: 767 DOI: 10.6093/978-88-6887-015-7
Publisher: FedOA - Federico II University Press
Subject: Therapeutics
Added to DOAB on : 2018-06-08 13:11:19
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For thousands of years, pharmacological knowledge coming from natural remedies, has been handed down from generation to generation, without any awareness of the ways in which preparations are made to face diseases. The advent of pharmaceutical chemistry and of the modern drug industry turned that lack of awareness into a scientific knowledge that changed the destiny of the human race. The twenty-eight chapters of this book, are taken from the lectures held by Professor Ettore Novellino every year in his course “Pharmaceutical Chemistry and Toxicology 2”. The first chapters address the basic notions of drugs, homeostasis, pharmacopoeia, and receptor; then, the different pharmaceutical classes are introduced by analyzing their pharmacological and chemical aspects. In particular, the structural study of the interaction between drugs and receptors or biological enzymes gives the fundamentals to connect the chemical and stereochemical properties of a compound family, with the biological activity, a correlation better known as Quantitative Structure-Activity Relationship (QSAR). Several examples of the synthesis of some of the most historically renown drugs, provided at the end of each chapter, integrate the book.

New Perspectives in Neurosteroids action: a Special Player Allopregnanolone

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195558 Year: Pages: 86 DOI: 10.3389/978-2-88919-555-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Early in the 80’s date the first observations on the existence of hormonal steroids that may be synthesized and act in the nervous system. In order to refer to these endogenous steroids, proved important to control both central and peripheral nervous system, it was proposed the term “neurosteroids” (NSs). Over the years, their importance in regulating the physiological functions of neuronal and glial cells increased progressively. These steroids can be involved in several pathophysiological conditions such as depression, anxiety, premenstrual syndrome (PMS), schizophrenia and Alzheimer disease. Among the different classes of NSs, the progestagens revealed particularly important. The progesterone metabolite 5a-pregnan-3a-ol-20-one, also named tetrahydroprogesterone or allopregnanolone (ALLO) was one of the first most important steroid that was originally shown to act as neurosteroid. ALLO is synthesized through the action of the 5aR-3a-HSD, which converts P into DHP and subsequently, via a bidirectional reaction, into ALLO. NSs exert complex effects in the nervous system through ‘classic’, genomic, and ‘non-classic’, non-genomic actions. ALLO displays a rapid ‘non-genomic’ effect, which mainly involves the potent modulation of the GABA type A (GABA-A) receptor function. Recently a membrane receptor has been identified as target for ALLO effects, i.e. the membrane progesterone receptors (mPRs) that are able to activate a signalling cascade through G protein dependent mechanisms. By these ways, ALLO is able to modulate several cell functions, acting as neurogenic molecule on neural progenitor cells, as well as by activating proliferation and differentiation of glial cells in the central and peripheral nervous system. In this topic, we review the most recent acquisitions in the field of neurosteroids, focusing our attention on ALLO because its effects on the physiology of neurons and glial cells of the central and peripheral nervous system are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues and for the treatment of neuropsychiatric disorders.

Molecular, Cellular and Model Organism Approaches for Understanding the Basis of Neurological Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451739 Year: Pages: 183 DOI: 10.3389/978-2-88945-173-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-08-28 14:01:09
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The advent of next-generation sequencing technologies has resulted in a remarkable increase our understanding of human and animal neurological disorders through the identification of disease causing or protective sequence variants. However, in many cases, robust disease models are required to understand how changes at the DNA, RNA or protein level affect neuronal and synaptic function, or key signalling pathways. In turn, these models may enable understanding of key disease processes and the identification of new targets for the medicines of the future. This e-book contains original research papers and reviews that highlight either the impact of next-generation sequencing in the understanding of neurological disorders, or utilise molecular, cellular, and whole-organism models to validate disease-causing or protective sequence variants.

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