The Implication of Glial Metabotropic Glutamate Receptors in Alzheimer’s Disease

2021 ◽  
Vol 20 ◽  
Author(s):  
Izabella B. Q. de Lima ◽  
Fabíola M. Ribeiro
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptors ◽  
Disease Progression ◽  
Glial Cells ◽  
Metabotropic Glutamate Receptors ◽  
Underlying Disease ◽  
App Processing ◽  
Metabotropic Glutamate ◽  
Brain Functions

: Alzheimer’s disease (AD) was first identified more than 100 years ago and, yet, aspects pertaining its origin as well as the mechanisms underlying disease progression are not well known. To this date, there is no therapeutic approach or disease modifying drug that could halt or at least delay disease progression. Until recently, glial cells were seen as secondary actors in brain homeostasis. Although this view was gradually refuted and the relevance of glial cells for the most diverse brain functions such as synaptic plasticity and neurotransmission was vastly proved, many aspects of its functioning as well as its role in pathological conditions remain poorly understood. Metabotropic glutamate receptors (mGluRs) in glial cells were shown to be involved in neuroinflammation and neurotoxicity. Besides its relevance for glial function, glutamatergic receptors are also central in the pathology of AD and recent studies have shown that glial mGluRs play a role in the establishment and progression of AD. Glial mGluRs influence AD-related alterations in Ca2+ signalling, APP processing and Aβ burden, as well as AD-related neurodegeneration. However, different types of mGluRs play different roles, depending on the cell type and brain region that is being analysed. Therefore, in this review we focus on the current understanding of glial mGluRs and their implication in AD, providing an insight for future therapeutics and identifying existing research gaps worth investigating.

The role of neuroglial metabotropic glutamate receptors in Alzheimer's disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Khaled S. Abd-Elrahman ◽  
Shaarika Sarasija ◽  
Stephen S. G. Ferguson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Expression Patterns ◽  
Neuronal Cell ◽  
Hyperphosphorylated Tau ◽  
Metabotropic Glutamate ◽  
Group I ◽  
The Brain

: Glutamate, the major excitatory neurotramitter 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.

scholarly journals Metabotropic Glutamate Receptors in Alzheimer’s Disease Synaptic Dysfunction: Therapeutic Opportunities and Hope for the Future

2020 ◽  
Vol 78 (4) ◽  
pp. 1345-1361
Author(s):  
Akriti Srivastava ◽  
Brati Das ◽  
Annie Y. Yao ◽  
Riqiang Yan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Early Event ◽  
Metabotropic Glutamate ◽  
Cognitive Improvement

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the presence of neuritic plaques and neurofibrillary tangles. The impaired synaptic plasticity and dendritic loss at the synaptic level is an early event associated with the AD pathogenesis. The abnormal accumulation of soluble oligomeric amyloid-β (Aβ), the major toxic component in amyloid plaques, is viewed to trigger synaptic dysfunctions through binding to several presynaptic and postsynaptic partners and thus to disrupt synaptic transmission. Over time, the abnormalities in neural transmission will result in cognitive deficits, which are commonly manifested as memory loss in AD patients. Synaptic plasticity is regulated through glutamate transmission, which is mediated by various glutamate receptors. Here we review recent progresses in the study of metabotropic glutamate receptors (mGluRs) in AD cognition. We will discuss the role of mGluRs in synaptic plasticity and their modulation as a possible strategy for AD cognitive improvement.

scholarly journals Group 1 Metabotropic Glutamate Receptors in Neurological and Psychiatric Diseases: Mechanisms and Prospective

2021 ◽  
pp. 107385842110210
Author(s):  
Li-Da Su ◽  
Na Wang ◽  
Junhai Han ◽  
Ying Shen
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Fine Tuning ◽  
Psychiatric Diseases ◽  
Metabotropic Glutamate ◽  
Group 1

Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that are activated by glutamate in the central nervous system (CNS). Basically, mGluRs contribute to fine-tuning of synaptic efficacy and control the accuracy and sharpness of neurotransmission. Among eight subtypes, mGluR1 and mGluR5 belong to group 1 (Gp1) family, and are implicated in multiple CNS disorders, such as Alzheimer’s disease, autism, Parkinson’s disease, and so on. In the present review, we systematically discussed underlying mechanisms and prospective of Gp1 mGluRs in a group of neurological and psychiatric diseases, including Alzheimer’s disease, Parkinson’s disease, autism spectrum disorder, epilepsy, Huntington’s disease, intellectual disability, Down’s syndrome, Rett syndrome, attention-deficit hyperactivity disorder, addiction, anxiety, nociception, schizophrenia, and depression, in order to provide more insights into the therapeutic potential of Gp1 mGluRs.

The role of group I metabotropic glutamate receptors in neuronal excitotoxicity in alzheimer’s disease

2005 ◽  
Vol 7 (1-2) ◽  
pp. 125-141 ◽  
Author(s):  
Vicky W. -W. Tsai ◽  
Heather L. Scott ◽  
Richard J. Lewis ◽  
Peter R. Dodd
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate ◽  
Group I

Glutamate Differently Modulates Metabotropic Glutamate Receptors in Neuronal and Glial Cells

2010 ◽  
Vol 35 (7) ◽  
pp. 1050-1063 ◽  
Author(s):  
Carlos Alberto Castillo ◽  
David Agustín León ◽  
Inmaculada Ballesteros-Yáñez ◽  
Inmaculada Iglesias ◽  
Mairena Martín ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Glial Cells ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate

scholarly journals Insomnia in Alzheimer’s Disease

2021 ◽  
Vol 7 (5) ◽  
pp. 1-3
Author(s):  
Joshua Roland ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Underlying Disease ◽  
Diagnosis And Treatment ◽  
Pharmacological Interventions ◽  
Disease Treatment ◽  
Treatment Data ◽  
Lack Of Sleep

Emerging data have suggested lack of sleep as being a possible contributor to the development of Alzheimer’s disease pathology, placing insomnia as a prospective target to positively impact underlying disease progression. Diagnosis and treatment of insomnia can be a challenge in general, with even more complexities occurring in the population of Alzheimer's disease. Treatment data is overall limited. However, multiple non-pharmacological and pharmacological interventions are available for consideration for management

Intracellular Ca2+ release mediated by metabotropic glutamate receptor activation in the leech giant glial cell.

1997 ◽  
Vol 200 (19) ◽  
pp. 2565-2573
Author(s):  
C Lohr ◽  
J W Deitmer
Keyword(s):  
Membrane Potential ◽  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Glial Cells ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Cyclopiazonic Acid ◽  
Receptor Activation ◽  
Atpase Inhibitor ◽  
Metabotropic Glutamate

We have investigated the effects of glutamate and glutamate receptor ligands on the intracellular free Ca2+ concentration ([Ca2+]i) and the membrane potential (Em) of single, identified neuropile glial cells in the central nervous system of the leech Hirudo medicinalis. Exposed glial cells of isolated ganglia were filled iontophoretically with the Ca2+ indicator dye Fura-2. Application of glutamate (200-500 mumoll-1) caused biphasic membrane potential shifts and increases in [Ca2+]i, which were only partly reduced by either removing extracellular Ca2+ or blocking ionotropic glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 50-100 mumol l-1. Metabotropic glutamate receptor (mGluR) ligands had the following rank of potency in inducing a rise in [Ca2+]i: quisqualate (QQ, 200 mumol l-1) > glutamate (200 mumol l-1) > L(+)2-amino-3-phosphonopropionic acid (L-AP3, 200 mumol l-1 > trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 400 mumol l-1). The mGluR-selective antagonist (RS)-alpha-methyl-4-carboxyphenylglycine [(RS)-MCPG, 1 mmol l-1] significantly reduced glutamate-evoked increases in [Ca2+]i by 20%. Incubation of the ganglia with the endoplasmic ATPase inhibitor cyclopiazonic acid (CPA, 10 mumol l-1) caused a significant (53%) reduction of glutamate-induced [Ca2+]i transients, while incubation with lithium ions (2 mmol l-1) resulted in a 46% reduction. The effects of depleting the Ca2+ stores with CPA and of CNQX were additive. We conclude that glutamate-induced [Ca2+]i transients were mediated by activation of both Ca(2+)-permeable ionotropic non-NMDA receptors and of metabotropic glutamate receptors leading to Ca2+ release from intracellular Ca2+ stores.

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