Therapeutic Potential Of Targeting Group Iii Metabotropic Glutamate Receptors As A Disease Modifying Strategy In The Treatment Of Parkinson S Disease
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Therapeutic Potential Of Targeting Group Iii Metabotropic Glutamate Receptors As A Disease Modifying Strategy In The Treatment Of Parkinson S Disease
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Author : Matthew Thomas John Betts
language : en
Publisher:
Release Date : 2011
Therapeutic Potential Of Targeting Group Iii Metabotropic Glutamate Receptors As A Disease Modifying Strategy In The Treatment Of Parkinson S Disease written by Matthew Thomas John Betts and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with Glutamic acid categories.
Parkinson's disease (PD) is characterised by a progressive loss of dopaminergic neurones from the SNpc, leading to numerous downstream changes in the basal ganglia circuitry. Overactivity of the glutamatergic subthalamonigral pathway may underlie this continual degeneration of the nigrostriatal system. With this in mind, this thesis examined whether selective activation of group III metabotropic glutamate receptor subtypes may offer a novel strategy to halt persistent degeneration in PD. -- Initial distribution studies revealed mGlu4 and 7 group III mGlu receptor subtypes, demonstrated particularly intense immunoreactivity in the SNpc, suggesting these receptors may be ideally positioned to provide neuroprotective effects. Therefore, the first objective was to confirm this neuroprotective possibility using a broad spectrum agonist, L-AP4. Sub-chronic supranigral L-AP4 treatment mediated functional neuroprotection against a unilateral 6-OHDA lesion of the SN, confirmed by behavioural assessment and post-mortem analyses. -- Secondly, the pharmacological identity of the group III mGlu receptor mediating this protective effect was examined. To investigate mGlu4 receptors, the novel mGlu4 selective PAM VU0155041, was also shown to provide functional neuroprotection in the 6-OHDA rat model to an almost comparable level reached with L-AP4. Whilst these neuroprotective effects are likely mediated by an inhibition of glutamate to protect from glutamate-mediated excitotoxicity, VUO15504 also led to a significant reduction in levels of GFAP and IBA-1 suggesting an additional anti-inflammatory action. Further studies revealed little evidence for co-localisation of mGlu4 receptors with GFAP in the SN suggesting this anti-inflammatory component likely reflects an indirect effect via stimulation of neuronal mGlu4 receptors.
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.
Modulation Of Basal Ganglia Function By Metabotropic Glutamate Receptors
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Author : Kari Anne Johnson
language : en
Publisher:
Release Date : 2013
Modulation Of Basal Ganglia Function By Metabotropic Glutamate Receptors written by Kari Anne Johnson and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with Electronic dissertations categories.
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.
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.
Leucine Rich Repeat Kinase 2 Lrrk2
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Author : Hardy J. Rideout
language : en
Publisher: Springer
Release Date : 2017-03-28
Leucine Rich Repeat Kinase 2 Lrrk2 written by Hardy J. Rideout and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-03-28 with Medical categories.
This is the first book to assemble the leading researchers in the field of LRRK2 biology and neurology and provide a snapshot of the current state of knowledge, encompassing all major aspects of its function and dysfunction. The contributors are experts in cell biology and physiology, neurobiology, and medicinal chemistry, bringing a multidisciplinary perspective on the gene and its role in disease. The book covers the identification of LRRK2 as a major contributor to the pathogenesis of Parkinson's Disease. It also discusses the current state of the field after a decade of research, putative normal physiological roles of LRRK2, and the various pathways that have been identified in the search for the mechanism(s) of its induction of neurodegeneration.
The Glutamate Gaba Glutamine Cycle
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Author : Arne Schousboe
language : en
Publisher: Springer
Release Date : 2016-11-25
The Glutamate Gaba Glutamine Cycle written by Arne Schousboe and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-11-25 with Medical categories.
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.
Parkinson S Disease Current And Future Therapeutics And Clinical Trials
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Author : Néstor Gálvez-Jiménez
language : en
Publisher: Cambridge University Press
Release Date : 2016-03-24
Parkinson S Disease Current And Future Therapeutics And Clinical Trials written by Néstor Gálvez-Jiménez and has been published by Cambridge University Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-03-24 with Medical categories.
This book emphasizes treatment options for Parkinson's disease, providing the necessary clinical and scientific basis for the foundations of solid therapeutics.
Neuropsychopharmacotherapy
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Author : Peter Riederer
language : en
Publisher: Springer Nature
Release Date : 2022-11-04
Neuropsychopharmacotherapy written by Peter Riederer and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-11-04 with Medical categories.
This book provides a reference guide describing the current status of medication in all major psychiatric and neurological indications, together with comparisons of pharmacological treatment strategies in clinical settings in Europe, USA, Japan and China. In addition, it highlights herbal medicine as used in China and Japan, as well as complementary medicine and nutritional aspects. This novel approach offers international readers a global approach in a single dedicated publication and is also a valuable resource for anyone interested in comparing treatments for psychiatric disorders in three different cultural areas. There are three volumes devoted to Basic Principles and General Aspects, offering a general overview of psychopharmacotherapy (Vol. 1); Classes, Drugs and Special Aspects covering the role of psychotropic drugs in the field of psychiatry and neurology (Vol. 2) and Applied Psychopharmacotherapy focusing on applied psychopharmacotherapy (Vol. 3). These books are invaluable to psychiatrists, neurologists, neuroscientists, medical practitioners and clinical psychologists.
Glutamate Related Biomarkers For Neuropsychiatric Disorders
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Author : Hsien-Yuan Lane
language : en
Publisher: Frontiers Media SA
Release Date : 2020-01-15
Glutamate Related Biomarkers For Neuropsychiatric Disorders written by Hsien-Yuan Lane 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 2020-01-15 with categories.