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Glutamatergic Receptors in Parkinson’s Disease

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Handbook of Neurotoxicity

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Abstract

Extracellular concentrations of the excitatory glutamate are maintained at relatively low levels to avoid an excessive activation of glutamate receptors (GluRs) that can trigger a cell death. This neuronal loss induced by hyperexcitation of GluRs has been associated with a wide range of acute and chronic neurological disorders such as Parkinson’s disease (PD). In fact, altered glutamatergic neurotransmission and metabolical dysfunction seems to be crucial in the pathophysiology of PD. Moreover, degeneration of dopamine nigral neurons of the substantia nigra pars compacta (SNpc) provokes striatal dopaminergic denervation and a cascade of functional modifications in the activity of basal ganglia nuclei including excitatory glutamate transmission. Glutamate receptors are divided into two distinct groups, ionotropic and metabotropic receptors. The ionotropic receptors (iGluRs) are further subdivided into three groups: (i) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), (ii) kainate, and (iii) N-methyl-d-aspartate (NMDA) receptor channels. The metabotropic receptors (mGluRs) are coupled to GTP-binding proteins (G proteins) and regulate the production of intracellular messengers. In this chapter, we review recent progress in the research of GluRs with special emphasis on the molecular diversity of the mGluR system and its implications in the physiopathology of PD. Finally, based on these evidences, we highlight possible therapeutic strategies that might be important to slow down the progression of PD as well as to modulate levodopa-induced dyskinesias.

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Acknowledgments

The authors thank the support by grants from the Spanish Ministry of Science (FIS 2010–02827), Fundación Séneca (FS/15329/PI/10), and CIBERNED (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas). Finally, the authors declare that there is no conflict of interests in the present work.

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Authors and Affiliations

  1. Clinical and Experimental Neuroscience (NiCE–CIBERNED), School of Medicine, Campus Espinardo, University of Murcia, 30071, Murcia, Spain

    A. Sampedro, V. Ortiz, A. Gómez & E. Fernández-Villalba

  2. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), School of Medicine, University of Murcia, Campus Mare Nostrum, 30071, Murcia, Spain

    A. Sampedro, V. Ortiz, A. Gómez & E. Fernández-Villalba

  3. Predepartmental Unit of Medicine, School of Health Sciences, Universitat Jaume I, Campus Riu Sec, 12100, Castellón, Spain

    E. Tarragón, J. E. Yuste, F. Ros-Bernal, C. M. Campuzano, C. M. Ros & M. T. Herrero

  4. Clinical and Experimental Neuroscience (NiCE–CIBERNED), School of Medicine, Campus de Espinardo, University of Murcia, 30071, Murcia, Spain

    E. Tarragón, J. E. Yuste, F. Ros-Bernal, C. M. Campuzano, C. M. Ros & M. T. Herrero

  5. Centro de Investigación Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), School of Medicine, University of Murcia, Campus Mare Nostrum, 30071, Murcia, Spain

    E. Tarragón, J. E. Yuste, F. Ros-Bernal, C. M. Campuzano, C. M. Ros & M. T. Herrero

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  1. A. Sampedro
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  3. J. E. Yuste
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  4. F. Ros-Bernal
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  9. E. Fernández-Villalba
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  10. M. T. Herrero
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Correspondence to M. T. Herrero .

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

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Sampedro, A. et al. (2014). Glutamatergic Receptors in Parkinson’s Disease. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_154

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