Glutamate Receptors and Excitotoxic Mechanisms in Alzheimer’s Disease

1999 ◽  
pp. 655-679
Author(s):  
James W. Geddes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptors

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.

Differential Regulation of Glutamate Receptors in Alzheimer’s Disease

Neurosignals ◽  
2002 ◽  
Vol 11 (5) ◽  
pp. 282-292 ◽  
Author(s):  
Hyoung-gon Lee ◽  
Xiongwei Zhu ◽  
Hossein A. Ghanbari ◽  
Osamu Ogawa ◽  
Arun K. Raina ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptors ◽  
Differential Regulation

scholarly journals Simulation of Ca2+ oscillations in astrocytes mediated by amyloid beta in Alzheimer’s disease

2020 ◽  
Author(s):  
Huayi Gao ◽  
Langzhou Liu ◽  
Shangbin Chen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Computational Model ◽  
Glutamate Receptors ◽  
Amyloid Beta ◽  
Amyloid Beta Peptide ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Beta Peptide ◽  
Intracellular Ca

AbstractDisruptions of astrocyte Ca2+ signaling is important in Alzheimer’s disease (AD) with the unclear mechanism of amyloid beta peptide (Aβ). We have modified our previous computational model of spontaneous Ca2+ oscillations in astrocytes to investigate the effects of Aβ on intracellular Ca2+ dynamics. The simulation results have shown consistence with the previous experiments. Aβ can increase the resting concentration of intracellular Ca2+ and change the regime of Ca2+ oscillations by activating L-type voltage-gated calcium channels and the metabolic glutamate receptors, or by increasing ryanodine receptors sensitivity and Ca2+ leakage, respectively. This work have provided a toolkit to study the influence of Aβ on intracellular Ca2+ dynamics in AD. It is helpful for understanding the toxic role of Aβ during the progression of AD.Statement of SignificanceAlzheimer’s disease (AD) is the most common neurodegenerative disease with the unclear mechanism of amyloid beta peptide (Aβ). This work have implemented a computational model to address the Ca2+ dynamics of astrocyte mediated by Aβ with the four different pathways: voltage-gated calcium channels, metabotropic glutamate receptors 5, ryanodine receptor channels and membrane leak. The Ca2+ oscillations and bifurcation diagram indicate that astrocytes exhibit ionic excitability mediated by Aβ and become the potential targets of Aβ neurotoxicity. We expect this shared computational model would advance the understanding of AD.

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.

scholarly journals Properties of glutamate receptors of Alzheimer's disease brain transplanted to frog oocytes

2007 ◽  
Vol 104 (8) ◽  
pp. 2956-2960 ◽  
Author(s):  
A. Bernareggi ◽  
Z. Duenas ◽  
J. M. Reyes-Ruiz ◽  
F. Ruzzier ◽  
R. Miledi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptors

scholarly journals Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer's disease

2009 ◽  
Vol 1292 ◽  
pp. 191-198 ◽  
Author(s):  
Yuesong Gong ◽  
Carol F. Lippa ◽  
Jinghua Zhu ◽  
Qishan Lin ◽  
Andrea L. Rosso
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptors
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