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Alzheimer's disease, β‐amyloid, glutamate, NMDA receptors and memantine – searching for the connections
Open accessAbstract
β‐amyloid (Aβ) is widely accepted to be one of the major pathomechanisms underlying Alzheimer's disease (AD), although there is presently lively debate regarding the relative roles of particular species/forms of this peptide. Most recent evidence indicates that soluble oligomers rather than plaques are the major cause of synaptic dysfunction and ultimately neurodegeneration. Soluble oligomeric Aβ has been shown to interact with several proteins, for example glutamatergic receptors of the NMDA type and proteins responsible for maintaining glutamate homeostasis such as uptake and release. As NMDA receptors are critically involved in neuronal plasticity including learning and memory, we felt that it would be valuable to provide an up to date review of the evidence connecting Aβ to these receptors and related neuronal plasticity. Strong support for the clinical relevance of such interactions is provided by the NMDA receptor antagonist memantine. This substance is the only NMDA receptor antagonist used clinically in the treatment of AD and therefore offers an excellent tool to facilitate translational extrapolations from in vitro studies through in vivo animal experiments to its ultimate clinical utility.
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“previous studies showing that A β deposition contributes to disturbed glutamatergic neurotransmission”
From Genetic variants of phospholipase C-γ2 alter the phenotype and function of microglia and confer differential risk for Alzheimer’s disease (2023) · cites this paper as [38]
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“oAβ has been reported to impair NMDAR-dependent synaptic LTP within hippocampal CA1 and dentate gyrus regions [65].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [65]
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“…pathological changes (i.e. receptor down-regulation as an adaptive change), as well as blatant loss of neuronal cells and synapses expressing these receptors as a long term consequence of chronic excitotoxicity (Geddes et al., 1986; Procter et al., 1989; Ninomiya et al., 1991; Hynd et al., 2001).”
BackgroundWelcome to the Journal of Neuroinflammation!
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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994
The Role of NMDA Receptors in Alzheimer’s Disease
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Dendritic Tau in Alzheimer’s Disease
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NMDA receptors and memory encoding
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Metadata
- Authors
- Danysz, W., & Parsons, C. G.
- Affiliations
- Merz (Germany) (DE)
- Corresponding author
- Parsons, Chris G
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2012-08-22
- Volume
- 167
- Issue
- 2
- Pages
- 324-352
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC3481041
- OpenAlex
- W1561114541
- Cited by
- 500
- References
- 260
- Citations by year
- 2026: 15 · 2025: 31 · 2024: 38 · 2023: 34 · 2022: 41 · 2021: 35 · 2020: 28 · 2019: 37 · 2018: 45 · 2017: 60 · 2016: 48 · 2015: 33 · 2014: 35 · 2013: 17 · 2012: 2
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, NMDA receptor, glutamate, glutamate homeostasis, synaptic dysfunction, neurodegeneration, neuroplasticity, learning and memory, memantine, NMDA receptor antagonists, amyloid plaques
- MeSH terms
- Alzheimer Disease, Humans, Memantine, Dopamine Agents, Receptors, N-Methyl-D-Aspartate, Amyloid beta-Peptides, Glutamic Acid
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