Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System

Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System

Author: Institute of Medicine

Publisher: National Academies Press

Published: 2011-08-05

Total Pages: 74

ISBN-13: 0309212219

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Glutamate is the most pervasive neurotransmitter in the central nervous system (CNS). Despite this fact, no validated biological markers, or biomarkers, currently exist for measuring glutamate pathology in CNS disorders or injuries. Glutamate dysfunction has been associated with an extensive range of nervous system diseases and disorders. Problems with how the neurotransmitter glutamate functions in the brain have been linked to a wide variety of disorders, including schizophrenia, Alzheimer's, substance abuse, and traumatic brain injury. These conditions are widespread, affecting a large portion of the United States population, and remain difficult to treat. Efforts to understand, treat, and prevent glutamate-related disorders can be aided by the identification of valid biomarkers. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop on June 21-22, 2010, to explore ways to accelerate the development, validation, and implementation of such biomarkers. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary investigates promising current and emerging technologies, and outlines strategies to procure resources and tools to advance drug development for associated nervous system disorders. Moreover, this report highlights presentations by expert panelists, and the open panel discussions that occurred during the workshop.


The Glutamate/GABA-Glutamine Cycle

The Glutamate/GABA-Glutamine Cycle

Author: Arne Schousboe

Publisher: Springer

Published: 2016-11-25

Total Pages: 420

ISBN-13: 3319450964

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Fundamental biochemical studies of basic brain metabolism focusing on the neuroactive amino acids glutamate and GABA combined with the seminal observation that one of the key enzymes, glutamine synthetase is localized in astroglial cells but not in neurons resulted in the formulation of the term “The Glutamate-Glutamine Cycle.” In this cycle glutamate released from neurons is taken up by surrounding astrocytes, amidated by the action of glutamine synthetase to glutamine which can be transferred back to the neurons. The conversion of glutamate to glutamine is like a stealth technology, hiding the glutamate molecule which would be highly toxic to neurons due to its excitotoxic action. This series of reactions require the concerted and precise interaction of a number of enzymes and plasma membrane transporters, and this volume provides in-depth descriptions of these processes. Obviously such a series of complicated reactions may well be prone to malfunction and therefore neurological diseases are likely to be associated with such malfunction of the enzymes and transporters involved in the cycle. These aspects are also discussed in several chapters of the book. A number of leading experts in neuroscience including intermediary metabolism, enzymology and transporter physiology have contributed to this book which provides comprehensive discussions of these different aspects of the functional importance of the glutamate-glutamine cycle coupling homeostasis of glutamatergic, excitatory neurotransmission to basic aspects of brain energy metabolism. This book will be of particular importance for students as well as professionals interested in these fundamental processes involved in brain function and dysfunction.


GABA And Glutamate

GABA And Glutamate

Author: Janko Samardzic

Publisher: BoD – Books on Demand

Published: 2018-03-21

Total Pages: 139

ISBN-13: 9535138219

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This book collates the contributions of a selected number of neuroscientists that are interested in the molecular, preclinical, and clinical aspects of neurotransmission research. The seven chapters in this book address the latest research/review data related to GABA/glutamate system's organization and function, the structure of receptors, subtypes and their ligands, as well as the translational approach and clinical implications. The book offers readers a rich collection of data regarding current and future applications of GABA and glutamate neurotransmission, including promising research strategies and potential clinical benefits.


GABA in the Nervous System

GABA in the Nervous System

Author: David L. Martin (M.D.)

Publisher:

Published: 2000

Total Pages: 538

ISBN-13:

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GABA in the Nervous System summarizes recent advances in understanding the role of GABA as a neurotransmitter. First discovered as an inhibitory signal in 1950, GABA may also fulfill a decisive role in diseases such as Parkinson's and Alzheimer's, stroke, and other clinical problems. This book provides a comprehensive understanding of GABA at both the molecular and systemic level. Each chapter provides a balanced view of current knowledge while referencing historical discoveries during the last half-century


The GABA Receptors

The GABA Receptors

Author: Salvatore J. Enna

Publisher: Humana Press

Published: 2007-07-19

Total Pages: 325

ISBN-13: 9781588298133

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The Gaba Receptors, Third Edition, presents a critical appraisal of our current understanding of the molecular, behavioral, biochemical, clinical, and pharmacological properties of GABA receptors. Emphasis is placed on exploring cutting-edge findings on the structureal properties of receptor sites, mechanisms of receptor expression, chemical agents that differentiate receptor subtypes, and phenotypes displayed by GABA receptor null mice. Chapters in this updated and expanded edition examine such topics as GABA receptor subypes, trafficking postsynaptic GABA receptors, GABA receptor mutations associated with idiopathic generalized epilepsies and febrile seizures, and GABA receptors as a potential therapeutic target.


Glutamate and GABA Receptors and Transporters

Glutamate and GABA Receptors and Transporters

Author: Jan Egebjerg

Publisher: CRC Press

Published: 2001-10-04

Total Pages: 456

ISBN-13: 9780748408818

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The ubiquitous presence of glutamate and GABA receptors in the nervous system makes these receptor systems pivotal to our understanding of neurotransmission. Cloning of the molecular components of these receptor systems has provided insights to the selectivity of many drugs and detailed characterisation at the molecular level is emerging. Moreover, continuous development of novel and selective drugs has revealed detailed information on the mechanism of receptor activation and regulation. However, the rapid development of different aspects of glutamate and GABA receptor research makes it increasingly difficult to establish a general view of the field. Studies of the receptors are a multi-disciplinary task employing many specialised techniques. This book conveys recent discoveries in a framework of the basic concepts in the field of glutamate and GABA receptor research. Glutamate and GABA Receptors and Transporters: Structure, Function and Pharmacology is suitable for postgraduate students studying ligand gated channels but also beneficial for industrial and academic research scientists in both the glutamate and GABA field. Universities offering programs in neuroscience, molecular pharmacology or medicinal chemistry will find this a valuable reference.


Magnesium in the Central Nervous System

Magnesium in the Central Nervous System

Author: Robert Vink

Publisher: University of Adelaide Press

Published: 2011

Total Pages: 354

ISBN-13: 0987073052

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The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.


Addiction

Addiction

Author: David Nutt

Publisher: Oxford University Press, USA

Published: 2013-09-26

Total Pages: 102

ISBN-13: 0199685703

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An essential reference for psychiatrists, clinical psychologists, trainees, and specialist nurses, as well as primary care physicians/GPs with a special interest in mental health conditions and other healthcare professionals.


Extrasynaptic GABAA Receptors

Extrasynaptic GABAA Receptors

Author: Adam C. Errington

Publisher: Springer

Published: 2014-09-22

Total Pages: 301

ISBN-13: 149391426X

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GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor-mediated inhibition, termed “tonic” inhibition, has been described. Whereas synaptic GABAA receptors underlie classical “phasic” GABAA receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This book highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.


Neural Plasticity and Memory

Neural Plasticity and Memory

Author: Federico Bermudez-Rattoni

Publisher: CRC Press

Published: 2007-04-17

Total Pages: 368

ISBN-13: 1420008412

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A comprehensive, multidisciplinary review, Neural Plasticity and Memory: From Genes to Brain Imaging provides an in-depth, up-to-date analysis of the study of the neurobiology of memory. Leading specialists share their scientific experience in the field, covering a wide range of topics where molecular, genetic, behavioral, and brain imaging techniq