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Metabotropic Glutamate Receptors and Neurodegeneration

  • Chapter
Excitotoxicity in Neurological Diseases

Abstract

Metabotropic glutamate (mGlu) receptors, which exert a modulatory effect on excitatory synaptic transmission, are considered as potential targets for neuroprotective drugs and the advent of potent and centrally available subtype-selective ligands has lead to an extensive investigation of the role of individual mGlu receptor subtypes in neurodegeneration. Pharmacological blockade of mGlu1 or -5 receptors or pharmacological activation of mGlu2/3 or mGlu4/7/8 receptors produces neuroprotection in a variety of in vitro or in vivo models. MGlu1 receptor antagonists are promising drugs for the treatment of brain ischemia or for the prophylaxis of neuronal damage induced by synaptic hyperactivity. MGlu5 receptor antagonists may limit neuronal damage induced by a hyperactivity of NMDA receptors, because mGlu5 and NMDA receptors are physically and functionally connected in neuronal membranes, suggesting a potential application of mGlu5 receptor antagonists in chronic neurodegenerative disorders, such as Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease (AD). MGlu2/3 receptor agonists inhibit glutamate release, and also promote the synthesis and release of neurotrophic factors in astrocytes. These drugs may therefore have a broad application as neuroprotective agents in a variety of eNS disorders. Finally, mGlu4/7/8 receptor agonists potently inhibit glutamate release and have a potential application in seizure disorders.

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Authors and Affiliations

  1. I.N.M. Neuromed, Pozzilli, Italy

    Valeria Bruno, Giuseppe Battaglia & Ferdinando Nicoletti

  2. Department of Human Physiology and Pharmacology, University of Rome “La Sapienza”, Rome, Italy

    Valeria Bruno & Ferdinando Nicoletti

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  1. Valeria Bruno
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  2. Giuseppe Battaglia
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  1. Department of Neurology and Neuroscience, University of Milano-Bicocca, Ospedale San Gerardo, Monza (Milano), Italy

    Carlo Ferrarese

  2. Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA

    M. Flint Beal

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Bruno, V., Battaglia, G., Nicoletti, F. (2004). Metabotropic Glutamate Receptors and Neurodegeneration. In: Ferrarese, C., Beal, M.F. (eds) Excitotoxicity in Neurological Diseases. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8959-8_6

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