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      Roles of Glutamate Receptors in Parkinson’s Disease

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          Abstract

          Parkinson’s disease is a progressive neurodegenerative disorder resulting from the degeneration of pigmented dopaminergic neurons in the substantia nigra pars compacta. It induces a series of functional modifications in the circuitry of the basal ganglia nuclei and leads to severe motor disturbances. The amino acid glutamate, as an excitatory neurotransmitter, plays a key role in the disruption of normal basal ganglia function regulated through the interaction with its receptor proteins. It has been proven that glutamate receptors participate in the modulation of neuronal excitability, transmitter release, and long-term synaptic plasticity, in addition to being related to the altered neurotransmission in Parkinson’s disease. Therefore, they are considered new targets for improving the therapeutic strategies used to treat Parkinson’s disease. In this review, we discuss the biological characteristics of these receptors and demonstrate the receptor-mediated neuroprotection in Parkinson’s disease. Pharmacological manipulation of these receptors during anti-Parkinsonian processes in both experimental studies and clinical trials are also summarized.

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          Most cited references119

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          Neuropathology of Parkinson disease.

          Parkinson's disease (PD) is characterized by bradykinesia, rigidity, postural instability and tremor. Several pathologic processes can produce this syndrome, but neurodegeneration accompanied by neuronal inclusions composed of α-synuclein (Lewy bodies) is considered the typical pathologic correlate of PD.
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            Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease.

            Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms.
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              Metabotropic glutamate receptors.

              Metabotropic glutamate receptors (mGlus) are a family of G-protein-coupled receptors activated by the neurotransmitter glutamate. Molecular cloning has revealed eight different subtypes (mGlu1-8) with distinct molecular and pharmacological properties. Multiplicity in this receptor family is further generated through alternative splicing. mGlus activate a multitude of signalling pathways important for modulating neuronal excitability, synaptic plasticity and feedback regulation of neurotransmitter release. In this review, we summarize anatomical findings (from our work and that of other laboratories) describing their distribution in the central nervous system. Recent evidence regarding the localization of these receptors in peripheral tissues will also be examined. The distinct regional, cellular and subcellular distribution of mGlus in the brain will be discussed in view of their relationship to neurotransmitter release sites and of possible functional implications.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                06 September 2019
                September 2019
                : 20
                : 18
                : 4391
                Affiliations
                [1 ]Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR999077, China
                [2 ]Department of Biology, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR 999077, China
                [3 ]Golden Meditech Center for NeuroRegeneration Sciences (GMCNS), Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR999077, China
                Author notes
                [* ]Correspondence: jksko@ 123456hkbu.edu.hk (J.K.-S.K.); kklyung@ 123456hkbu.edu.hk (K.K.-L.Y.); Tel.: +852-3411-2907 (J.K.-S.K.); +852-3411-7060 (K.K.-L.Y.); Fax: +852-3411-2461 (J.K.-S.K.); +852-3411-5995 (K.K.-L.Y.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-3842-6408
                Article
                ijms-20-04391
                10.3390/ijms20184391
                6769661
                31500132
                a9b7042d-864e-48fe-beb6-15e352c88ce5
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 August 2019
                : 27 August 2019
                Categories
                Review

                Molecular biology
                parkinson’s disease,glutamate receptors,nmda receptor,mglur4,mglur5
                Molecular biology
                parkinson’s disease, glutamate receptors, nmda receptor, mglur4, mglur5

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