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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

The Role of Neuroglial Metabotropic Glutamate Receptors in Alzheimer’s Disease

Author(s): Khaled S. Abd-Elrahman*, Shaarika Sarasija and Stephen S.G. Ferguson*

Volume 21, Issue 2, 2023

Published on: 28 March, 2022

Page: [273 - 283] Pages: 11

DOI: 10.2174/1570159X19666210916102638

Price: $65

Abstract

Glutamate, the major excitatory neurotransmitter in the brain exerts its effects via both ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). There are three subgroups of mGluRs, pre-synaptic Group II and Group III mGluRs and post-synaptic Group I mGluRs. mGluRs are ubiquitously expressed in the brain and their activation is poised upstream of a myriad of signaling pathways, resulting in their implication in the pathogenesis of various neurodegenerative diseases including, Alzheimer’s Disease (AD). While the exact mechanism of AD etiology remains elusive, β-amyloid (Aβ) plaques and hyperphosphorylated tau tangles remain the histopathological hallmarks of AD. Though less electrically excitable, neuroglia are a major non-neuronal cell type in the brain and are composed of astrocytes, microglia, and oligodendrocytes. Astrocytes, microglia, and oligodendrocytes provide structural and metabolic support, active immune defence, and axonal support and sheathing, respectively. Interestingly, Aβ and hyperphosphorylated tau are known to disrupt the neuroglial homeostasis in the brain, pushing them towards a more neurotoxic state. In this review, we discuss what is currently known regarding the expression patterns of various mGluRs in neuroglia and how Aβ and tau alter the normal mGluR function in the neuroglia and contribute to the pathophysiology of AD.

Keywords: mGluR, GPCR, tau, amyloid beta, neurodegeneration, astrocytes, microglia, oligodendrocytes.

Graphical Abstract

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