Cited by 550Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismCell death mechanisms and regulation

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Molecular Mechanisms of Glutamate Receptor-Mediated Excitotoxic Neuronal Cell Death

Sattler, Rita, Tymianski, Michael·2001·Molecular Neurobiology

DOI 10.1385/mn:24:1-3:107

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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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Authors: Sattler, R., & Tymianski, M.
Affiliations: Howard Hughes Medical Institute (US)
Toronto Western Hospital (CA)
Corresponding author: Sattler, Rita
ORCID: Sattler, Rita
Tymianski, Michael
Venue: Molecular Neurobiology
Publisher: Springer Science and Business Media LLC
Published: 2001
Volume: 24
Issue: 1-3
Pages: 107-130
ISSN: 0893-7648 (ISSN-L)
DOI: 10.1385/mn:24:1-3:107
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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Molecular Mechanisms of Glutamate Receptor-Mediated Excitotoxic Neuronal Cell Death

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