Role of Glutamate and NMDA Receptors in Alzheimer’s Disease
Open accessAbstract
Excitatory glutamatergic neurotransmission via N-methyl-d-aspartate receptor (NMDAR) is critical for synaptic plasticity and survival of neurons. However, excessive NMDAR activity causes excitotoxicity and promotes cell death, underlying a potential mechanism of neurodegeneration occurred in Alzheimer’s disease (AD). Studies indicate that the distinct outcomes of NMDAR-mediated responses are induced by regionalized receptor activities, followed by different downstream signaling pathways. The activation of synaptic NMDARs initiates plasticity and stimulates cell survival. In contrast, the activation of extrasynaptic NMDARs promotes cell death and thus contributes to the etiology of AD, which can be blocked by an AD drug, memantine, an NMDAR antagonist that selectively blocks the function of extrasynaptic NMDARs.
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Glutamic acid targets SLC25A18, a glutamate transporter involved in excitatory signaling in neurons.
“Glutamic acid (DB00142) targets SLC25A18, a glutamate transporter86 and is involved in excitatory signaling in neurons87.”
From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [87]
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- Authors
- Wang, R., & Reddy, P. H.
- Affiliations
- Texas Tech University Health Sciences Center (US)
- Texas Tech University (US)
- Corresponding author
- Wang, Rui
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2016-09-23
- Volume
- 57
- Issue
- 4
- Pages
- 1041-1048
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC5791143
- OpenAlex
- W2521991649
- Cited by
- 1,009
- References
- 13
- Citations by year
- 2026: 83 · 2025: 136 · 2024: 153 · 2023: 160 · 2022: 139 · 2021: 144 · 2020: 112 · 2019: 61 · 2018: 15 · 2017: 5 · 2016: 1
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG042178, R01AG047812)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, NMDA receptor
- MeSH terms
- Alzheimer Disease, Humans, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate
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