Mechanism of neuroprotective effect of mGluR4 agonists

Natalya V Avdeeva,Ivan V Golubev,Ol'Ga A Osipova,Oleg S Gudyrev,Svetlana A Sidorova

doi:10.3897/rrpharmacology.5.36565

Abstract

Introduction: This review of literature is to demonstrate a role of group III metabotropic glutamate receptors in maintaining the level of extracellular glutamate in ischemic stroke and neurodegenerative diseases. Metabotropic glutamate receptors: mGluRs are classified into three groups. It is suggested that the activation of mGluR4 may have a neuroprotective effect. Role of excitotoxicity in the development and severity of various brain diseases: An increase in the concentrationьof intracellular Ca2+ is the result of excessive accumulation of glutamate in the extracellular space. And a death of nerve cells occurs after a sequence of biochemical reactions, which was called excitotoxicity. It is followed by an imbalance between glutamatergic excitation and GABA-ergic inhibition. As a result of untimely activation of the inhibitory mechanisms, the accumulation of extracellular glutamate, and consequently the death of neurons, continues, which leads to more severe manifestations of the cerebral ischemia. Role of modulation of mGluRs activity in neuroprotection: The literature describes a large number of studies proving that inhibition of hyperactive glutamatergic transmission has a neuroprotective effect. The most likely mechanisms of neuroprotection are inhibition of glutamate production in the substantia nigra, which in turn protects against glutamate-mediated excitotoxicity, and the reduction of the inflammatory effects. Anti-inflammatory effect of mGluR4 agonists in the mechanism of neuroprotective action: The astroglial component may contribute to the protective action of mGluR4 modulators, since astrocytes and microglia have mGluR4. Conclusion: mGluR4 agonists have the neuroprotective and anti-inflammatory effects.

Highlights

This review of literature is to demonstrate a role of group III metabotropic glutamate receptors in maintaining the level of extracellular glutamate in ischemic stroke and neurodegenerative diseases
Experimental studies have shown the presence of the neuroprotective effect of group III mGluRs agonists
In haloperidol and reserpine models of parkinsonism the administration of mGluR4 agonists resulted in a decrease in the symptoms and signs (Niswender and Conn 2010)

Summary

Introduction

This review of literature is to demonstrate a role of group III metabotropic glutamate receptors in maintaining the level of extracellular glutamate in ischemic stroke and neurodegenerative diseases. Role of excitotoxicity in the development and severity of various brain diseases: An increase in the concentration of intracellular Ca2+ is the result of excessive accumulation of glutamate in the extracellular space. As a result of untimely activation of the inhibitory mechanisms, the accumulation of extracellular glutamate, and the death of neurons, continues, which leads to more severe manifestations of the cerebral ischemia. Avdeeva NV et al.: Mechanism of neuroprotective effect of mGluR4 agonists a pathway, which activate a number of enzymes that damage neurons. The purpose of this article is to demonstrate the role of mGluRs in maintaining the level of extracellular glutamate in excitotoxicity or cerebral ischemia (Moyanova et al 2011)

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Conclusion