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Molecular Mechanisms of Glutamate Receptor-Mediated Excitotoxic Neuronal Cell Death
Abstract
Excitotoxicity is one of the most extensively studied processes of neuronal cell death, and plays an important role in many central nervous system (CNS) diseases, including CNS ischemia, trauma, and neurodegenerative disorders. First described by Olney, excitotoxicity was later characterized as an excessive synaptic release of glutamate, which in turn activates postsynaptic glutamate receptors. While almost every glutamate receptor subtype has been implicated in mediating excitotoxic cell death, it is generally accepted that the N-methyl-D-aspartate (NMDA) subtypes play a major role, mainly owing to their high calcium (Ca2+) permeability. However, other glutamate receptor subtypes such as 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionate (AMPA) or kainate receptors have also been attributed a critical role in mediating excitotoxic neuronal cell death. Although the molecular basis of glutamate toxicity is uncertain, there is general agreement that it is in large part Ca(2+)-dependent. The present review is aimed at summarizing the molecular mechanisms of NMDA receptor and AMPA/kainate receptor-mediated excitotoxic neuronal cell death.
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“Excitotoxicity is considered to be a major mechanism of neuronal death that occurs due to intracellular calcium overload followed by the activation of various cell death pathways41.”
From Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke (2016) · cites this paper as [41]
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Singhal, S., Lawrence, J. M., Salt, T. E., Khaw, P. T., & Limb, G. A. (2009) · Experimental Eye Research · doi:10.1016/j.exer.2009.11.008 · Cited by 41
Metadata
- Authors
- Sattler, R., & Tymianski, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Toronto Western Hospital (CA)
- Corresponding author
- Sattler, Rita
- Venue
- Molecular Neurobiology
- Published
- 2001
- Volume
- 24
- Issue
- 1-3
- Pages
- 107-130
- ISSN
- 0893-7648 (ISSN-L)
- OpenAlex
- W2027397876
- Cited by
- 537
- References
- 197
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 11 · 2023: 15 · 2022: 14 · 2021: 15 · 2020: 22 · 2019: 18 · 2018: 23 · 2017: 22 · 2016: 25 · 2015: 27 · 2014: 23 · 2013: 22 · 2012: 24
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns039060-03)
- National Institute of Neurological Disorders and Stroke (R01 NS 39060)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- excitotoxicity, neuronal cell death, glutamate receptors, NMDA receptor, AMPA receptors, kainate receptors, calcium signaling, neurodegenerative diseases
- MeSH terms
- Animals, Central Nervous System Diseases, Humans, Neurons, Neurotoxins, Cell Death, Receptors, Glutamate
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