Metabotrobic Glutamate Receptor Mglur4 As A Novel Target For Parkinson S Disease
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Metabotropic Glutamate Receptor Mglur4 As A Novel Target For Parkinson S Disease
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Author :
language : en
Publisher:
Release Date : 2001
Metabotropic Glutamate Receptor Mglur4 As A Novel Target For Parkinson S Disease written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001 with categories.
Parkinson's disease (PD) is characterized by a loss of substantia nigra dopaminergic neurons. Here we describe our progress in understanding the role of metabotropic glutamate receptors (mGluRs) as a novel target for the treatment of PD. We have localized mGluR4 in basal ganglia structures, and explored its role in mediating the electrophysiological effects of glutamate in rat brain slices. We have explored the efficacy of mGluR drugs in relieving motor symptoms in hemiparkinsonian monkeys. We found that group III mGluRs are presynaptic on striatal-pallidal terminals and that they mediate a reduction in IPSC amplitude in the SNr. They also pre-synaptically inhibit EPSCs at the STN-SNr synapse. In this study, we have found that groups I and II mGluRs also have critical roles in regulating basal ganglia function. Group II mGluRs mediate a presynaptic reduction of EPSCs in the SNr and group II agonist LY354740 reverses catalepsy in a rodent model of PD. Pre- and Post-synaptic group I mGluRs are involved in regulation of basal ganglia output nuclei by both excitation and disinhibition. Furthermore, comprehensive characterization of the roles of mGluRs in the basal ganglia raises the possibility that they may provide targets for novel therapeutic agents for treatment of PD.
Metabotrobic Glutamate Receptor Mglur4 As A Novel Target For Parkinson S Disease
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Author :
language : en
Publisher:
Release Date : 1999
Metabotrobic Glutamate Receptor Mglur4 As A Novel Target For Parkinson S Disease written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999 with categories.
The symptoms of Parkinson's disease (PD) are associated with a loss of substantia nigra dopaminergic neurons involved in modulation of function of the basal ganglia (BG) . This report describes our progress in understanding the role of metabotropic glutamate receptors (mGluRs) as a novel target for the treatment of PD. Specifically, our aims are to localize mGluR4 in rat and monkey basal ganglia structures, to determine the role of this receptor vs. other subtypes in mediating the electrophysiological effects of glutamate in rat brain slices, and to determine the efficacy of drugs aimed mGluRs in relieving motor symptoms in hemi-parkinsonian monkeys. We found that group III mGluRs are presynaptic on striatal-pallidal terminals and that they mediate a reduction in IPSC amplitude in the SNr. Group III mGluRs also presynaptically inhibit EPSCs at the STN-SNr synapse. Group II mGluRs were found to mediate a presynaptic reduction of EPSCs in the SNr and group II agonist LY354740 reverses catalepsy in an animal model of PD. Furthermore, as these studies progress, the distribution and physiological roles of mGluRs in the BG raises the possibility that these receptors may provide targets for novel therapeutic agents for treatment of PD and related disorders.
Characterisation Of Metabotropic Glutamate Receptor 4 As A Therapeutic Target In Parkinson S Disease
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Author : Elizabeth Mann
language : en
Publisher:
Release Date : 2019
Characterisation Of Metabotropic Glutamate Receptor 4 As A Therapeutic Target In Parkinson S Disease written by Elizabeth Mann and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with categories.
In addition to studies on mGluR4, some model characterisation work was also carried out. Anxiety and craving, non-motor symptoms commonly seen in PD patients, were observed in the bilateral version of the early stage rat model of PD. This could indicate that the model is useful for examining mGluR4 agonists and other potential treatments of PD more fully, in a holistic sense, rather than the traditional methods of separating out the treatment of motor and non-motor symptoms. In conclusion, a systemically-administered agonist of mGluR4 showed promise in the treatment of neurodegeneration in an early-stage model of PD in rats. This appears to have a number of underlying mechanisms including some modulation of inflammation and also transcriptional changes to genes which have been shown to affect neurodegeneration and neuroprotection. Furthermore, this agonist also has anti-Parkinsonian potential without causing dyskinesia - mGluR4 is therefore a suitable and promising target for further research in PD.
Characterisation Of Metabotropic Glutamate Receptor 4 As A Therapeutic Target In Parkinson S Disease
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Author : Elizabeth Caroline Mann
language : en
Publisher:
Release Date : 2019
Characterisation Of Metabotropic Glutamate Receptor 4 As A Therapeutic Target In Parkinson S Disease written by Elizabeth Caroline Mann and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with categories.
The Metabotropic Glutamate Receptors
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Author : P. Jeffrey Conn
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-03-09
The Metabotropic Glutamate Receptors written by P. Jeffrey Conn and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-03-09 with Medical categories.
The Metabotropic Glutamate Receptors offers state-of-the-art summaries and reviews of virtually everything known today about metabotropic glutamate receptors (mGluRs), including their molecular biology, pharmacology, anatomical distribution, and physiological and pathological roles. Illuminating the overall role played by this crucial class of receptors in brain function, the book also pinpoints those areas in which there is the greatest continuing need for focused research. Because mGluRs have the potential for participating in virtually all known functions of the central nervous system (CNS), the opportunity now exists to develop pharmacological agents that can potentially alter many brain disease processes by selective interaction with precise CNS functions. With its critical and insightful reviews, The Metabotropic Glutamate Receptors will immediately become your essential key to the development of novel treatment strategies for the widest variety of neurological disorders.
Investigating Group Iii Metabotropic Glutamate Receptors As Novel Therapeutic Targets In Parkinson S Disease And Levodopa Induced Dyskinesia
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Author :
language : en
Publisher:
Release Date : 2014
Investigating Group Iii Metabotropic Glutamate Receptors As Novel Therapeutic Targets In Parkinson S Disease And Levodopa Induced Dyskinesia written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with Movement disorders categories.
Finally, since other antiglutamatergic strategies have proven successful, we investigated mGiu4 activation as a means to inhibit L-DOPA-induced dyskinesia expression or development in rodents. While this approach was ineffective at reversing established dyskinesia there was a hint that it might be efficacious at delaying the onset of this complication that will be worth investigating further. In conclusion, targeting the mGiu4 receptor has shown some beneficial effects in relation to Parkinson's disease but much remains to be discovered about the actions of these agents both within and outside of the basal ganglia before any clear potential is revealed.
Metabotropic Glutamate Receptors And Neurological Psychiatric Disorders
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Author : Enza Palazzo
language : en
Publisher: Frontiers Media SA
Release Date : 2019-06-19
Metabotropic Glutamate Receptors And Neurological Psychiatric Disorders written by Enza Palazzo and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-06-19 with categories.
Considering that neurological and psychiatric illnesses do not still have efficient therapies and are becoming increasingly widespread, the search for novel targets appears fundamental. Neuroinflammation, alterations in adult neurogenesis and excitotoxicity, all associated with glutamate transmission dysfunction, are key components of the pathogenetic mechanisms underlying neuropsychiatric illnesses. Counteracting the neurotoxic actions of glutamate through the modulatory actions of metabotropic glutamate receptors (mGluRs), represents a rational intervention that offers tolerability compatible with clinical therapy. Their suitability as targets for developing novel therapies is also based on the fact that mGluRs are found abundantly expressed in synapses of the central nervous system (CNS) that are considered critical in certain neurological and psychiatric disorders. Moreover, recently there has been an exponential development of selective ligands, especially positive and negative allosteric modulators, which by binding to less conserved transmembrane domain sequences ensure, besides a good permeability in the CNS, an adequate selectivity for each mGluR subtype. The eBook “Metabotropic Glutamate Receptors and Neurological/Psychiatric Disorders”, collects contributes (original and review articles) on the beneficial effects of positive and negative allosteric modulators of mGluRs in animal models of neurological and psychiatric diseases from renown experts in the field. The hope is that the effort of both Editors and Contributors of this eBook confirms the unlimited potential of mGluRs in CNS diseases and generate a collaborative discussion on the state of art, overall trends, novel strategies, and future direction of this attractive field of research.
Primer On Cerebrovascular Diseases
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Author : K. Michael Welch
language : en
Publisher: Academic Press
Release Date : 1997-04-24
Primer On Cerebrovascular Diseases written by K. Michael Welch and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1997-04-24 with Medical categories.
Primer on Cerebrovascular Diseases is a handy reference source for scientists, students, and physicians needing reliable, up-to-date information on basic mechanisms, physiology, pathophysiology, and medical issues related to brain vasculature. The book consists of short, specific chapters written by international experts on cerebral vasculature, and presents the information in a comprehensive and easily accessible manner. The book also contains valuable information on practical applications of basic research. Presents topics in a comprehensive and accessible format Written by international authorities on cerebral vasculature Provides practical applications for researchers
Glial Neuronal Signaling
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Author : Glenn I. Hatton
language : en
Publisher: Springer Science & Business Media
Release Date : 2004-05-31
Glial Neuronal Signaling written by Glenn I. Hatton and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004-05-31 with Medical categories.
Glial Neuronal Signaling fills a need for a monograph/textbook to be used in advanced courses or graduate seminars aimed at exploring glial-neuronal interactions. Even experts in the field will find useful the authoritative summaries of evidence on ion channels and transporters in glia, genes involved in signaling during development, metabolic cross talk and cooperation between astrocytes and neurons, to mention but a few of the timely summaries of a wide range of glial-neuronal interactions. The chapters are written by the top researchers in the field of glial-neuronal signaling, and cover the most current advances in this field. The book will also be of value to the workers in the field of cell biology in general. When we think about the brain we usually think about neurons. Although there are 100 billion neurons in mammalian brain, these cells do not constitute a majority. Quite the contrary, glial cells and other non-neuronal cells are 10-50 times more numerous than neurons. This book is meant to integrate the emerging body of information that has been accumulating, revealing the interactive nature of the brain's two major neural cell types, neurons and glia, in brain function.
Human Drug Targets
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Author : Edward D. Zanders
language : en
Publisher: John Wiley & Sons
Release Date : 2015-12-14
Human Drug Targets written by Edward D. Zanders and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-12-14 with Science categories.
The identification of drug targets in a given disease has been central to pharmaceutical research from the latter half of the 20th century right up to the modern genomics era. Human Drug Targets provides an essential guide to one of the most important aspects of drug discovery – the identification of suitable protein and RNA targets prior to the creation of drug development candidates. The first part of the book consists of introductory chapters that provide the background to drug target discovery and highlight the way in which these targets have been organised into online databases. It also includes a user’s guide to the list of entries that forms the bulk of the book. Since this is not designed to be a compendium of drugs, the emphasis will be on the known (or speculated) biological role of the targets and not on the issues associated with pharmaceutical development. The objective is to provide just enough information to be informative and prompt further searches, while keeping the amount of text for each of the many entries to a minimum. Human Drug Targets will prove invaluable to those drug discovery professionals, in both industry and academia, who need to make some sense of the bewildering array of online information sources on current and potential human drug targets. As well as creating order out of a complex target landscape, the book will act as an ideas generator for potentially novel targets that might form the basis of future discovery projects.