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.


Molecular Mechanisms of Synaptogenesis

Molecular Mechanisms of Synaptogenesis

Author: Alexander Dityatev

Publisher: Springer Science & Business Media

Published: 2006-11-24

Total Pages: 504

ISBN-13: 038732562X

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This book provides a new compilation of information that link changes in the basic structure of synapses and brain diseases. The book shows that specific secreted proteins, and short peptide mimicking the function of neural cell adhesion molecules can significantly enhance the formation of synapses in the brain. It describes recent advances in research that lay necessary scientific groundwork to develop pharmacological treatments.


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


Glutamate

Glutamate

Author:

Publisher:

Published: 2000

Total Pages: 291

ISBN-13: 9780444903402

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The volume presents a comprehensive and up-to-date treatise of the glutamatergic synapse and its environment. Particular emphasis is on the localizations of the molecular constituents of the synaptic machinery. Immunogold and other high-resolution methods are used extensively. Each chapter presents new data that have not previously been reviewed. The material presented forms the basis for work directed to understanding the functional properties of excitatory synapses in greater depth, to discover mechanisms of neurological and psychiatric disorders and novel methods for treatment. Chapter 1 deals with the transmitter molecule itself, mechanisms of release and pathways for glutamate synthesis. The anatomy of glutamatergic nerve projection pathways in different brain regions is dealt with. In Chapter 2, focus is on aspartate, the enigmatic congener of glutamate, and its possible role in excitatory neurotransmission. Chapters 3 through 6 deal with glutamate receptors. Metabotropic glutamate receptors are presented in Chapter 3. Chapter 4 presents an in situ hybridization atlas of the different classes of ionotropic glutamate receptors. The localizations of these receptors at the regional and synaptic level are presented in Chapter 5. The ways in which the receptors are brought to the synapse and held in position are the subject of Chapter 6. Chapter 7 deals with the enzymes responsible for formation and catabolism of glutamate. In Chapter 8, the regulation of extracellular glutamate levels by glutamate transporters is discussed. The final two chapters of the volume focus on two "model synapses" that, due to special features, lend themselves particularly well to demonstrating properties of glutamatergic synapses. The hair cell-to-afferent nerve terminal synapses in the inner ear (Chapter 9), with their supporting cells, share essential properties with glutamatergic synapses in the central nervous system. The salient features of the latter are illustrated by the synapses of the giant reticulo-spinal axons of the lamprey, used to unravel molecular mechanisms of the cycling of synaptic vesicles (Chapter 10)


Metabotropic Glutamate Receptors

Metabotropic Glutamate Receptors

Author: M. Foster Olive

Publisher: Nova Science Publishers

Published: 2014

Total Pages: 0

ISBN-13: 9781631174513

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As the most abundant excitatory neurotransmitter in the brain, glutamate plays an important role in numerous aspects of normal and pathological brain function. This book provides an overview of the role of metabotropic glutamate receptors (mGluRs) in basic brain functioning, such as autonomic regulation, synaptic plasticity, and learning and memory. Also provided are up-to-date summaries of recent progress towards identifying how mGluRs both mediate and represent novel pharmacotherapeutic targets for the treatment of various neurological and neuropsychiatric disorders, such as depression, anxiety, schizophrenia, amyloidogenic disorders and substance abuse.


Translational Research in Traumatic Brain Injury

Translational Research in Traumatic Brain Injury

Author: Daniel Laskowitz

Publisher: CRC Press

Published: 2016-04-21

Total Pages: 388

ISBN-13: 1498766579

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Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the developme


The Sticky Synapse

The Sticky Synapse

Author: Michael Hortsch

Publisher: Springer Science & Business Media

Published: 2009-06-07

Total Pages: 451

ISBN-13: 0387927085

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The molecular mechanisms, which are responsible for the functional differences between the various types of neuronal synapses, have become one of the central themes of modern neurobiology. It is becoming increasingly clear that a misregulation of synaptogenesis and synaptic remodeling and dysfunctional neuronal synapses are at the heart of several human diseases, both neurological disorders and psychiatric conditions. As synapses present specialized cellular junctions between neurons and their target cells, it may not come as a surprise that neural cell adhesion molecules (CAMs) are of special importance for the genesis and the maintenance of synaptic connections. Genes encoding adhesive molecules make up a significant portion of the human genome, and neural CAMs even have been postulated to be a major factor in the evolution of the human brain. These are just some of the many reasons why we thought a book on neural CAMs and their role in establishing and maintaining neuronal synapses would be highly appropriate for summarizing our current state of knowledge. Without question, over the near future, additional adhesive proteins will join the ranks of synaptic CAMs and our knowledge, and how these molecules enable neurons and their targets to communicate effectively will grow.


Synaptic Stress and Pathogenesis of Neuropsychiatric Disorders

Synaptic Stress and Pathogenesis of Neuropsychiatric Disorders

Author: Maurizio Popoli

Publisher: Springer

Published: 2016-09-03

Total Pages: 0

ISBN-13: 9781493946327

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Recent studies show that changes in Glutamate/GABA synapses and related pathways may determine whether the synaptic plasticity that occurs as a response to stress is adaptive or maladaptive. Findings have shed new light on the mechanisms that determine the effects of stress on cognitive and affective function. Researchers have brought a wide range of techniques to bear on the study of this problem, including cutting-edge live imaging techniques, electrophysiology, glutamate release from isolated live synaptic terminals, development of transgenic and animal models and new behavioral methods. This book provides an overview of these recent findings and of the techniques used as well as a discussion of how the molecular, cellular, and functional effects of stress may trigger or precipitate neuropsychiatric disorders such as depression, schizophrenia, anxiety and PTSD.


Structural and Functional Organization of the Synapse

Structural and Functional Organization of the Synapse

Author: Johannes W. Hell

Publisher: Springer

Published: 2016-05-01

Total Pages: 820

ISBN-13: 9781489979056

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The synapse is a fascinating structure for many reasons. Biologically, it is an exquisitely organized subcellular compartment that has a remarkable capacity for fidelity and endurance. Computationally, synapses play a central role in signal transmission and processing that represent evolution s solution to learning and memory. Nervous systems, including our own brains, possess an extraordinary capacity for adaptation and memory because the synapse, not the neuron, constitutes the basic unit for information storage. Because the molecular complexities underlying signal processing and information storage must occur within the tiny space of the synapse, the precise molecular organization of proteins, lipids, and membranes at the synapse is paramount. Given the central role of the synapse in neuronal communication, it comes as no surprise that dysregulation of the synapse accounts for many, if not most, neurological and psychiatric disorders. Clinically, the synapse thus constitutes a prime target for treatments of these diseases. It is for these reasons that we have chosen to focus our work on deciphering the structural and functional organization of the synapse. We have assembled leaders in the field of synapse biology to describe and distill the wonders and mysteries of the synapse. This book provides a fundamental description of the synapse developed over many decades by numerous investigators, paired with recent insight into new aspects of synapse structure and function that is still in flux and at the cutting edge of research."