Title:The Role of Neuroglial Metabotropic Glutamate Receptors in Alzheimer’s
Disease
Volume: 21
Issue: 2
Author(s): Khaled S. Abd-Elrahman*, Shaarika Sarasija and Stephen S.G. Ferguson*
Affiliation:
- Department of Cellular and Molecular Medicine, University of Ottawa 451 Smyth Road, Ottawa K1H 8M5, Ontario,
Canada
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria
21521, Egypt
- Department of Cellular and Molecular Medicine, University of Ottawa 451 Smyth Road, Ottawa K1H 8M5, Ontario,
Canada
Keywords:
mGluR, GPCR, tau, amyloid beta, neurodegeneration, astrocytes, microglia, oligodendrocytes.
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.