Cited by 372Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismReceptor Mechanisms and Signaling

N-Methyl-d-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease

Waxman, Elisa A., Lynch, David R.·2005·The Neuroscientist

Abstract

N-methyl-D-aspartate (NMDA) receptors are the major mediator of excitotoxicity. Although physiological activation of the NMDA receptor is necessary for cell survival, overactivation is a signal for cell death. Several pathways are activated through NMDA receptor stimulation, most of which can contribute to excitotoxicity. These include events leading to mitochondrial dysfunction, activation of calcium-dependent enzymes, and activation of mitogen-activated protein kinase pathways. Understanding the role of these mechanisms is important in developing agents that block excitotoxicity without inhibiting functions necessary for survival. NMDA receptor subtypes may be responsible for mediating separate pathways, and subtype-specific inhibition has shown promising results in some neurological models. This review examines the roles of NMDA receptor subtypes in excitotoxicity and neurological disorders.

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Crossref · 10.1177/1073858404269012

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Authors
Waxman, E. A., & Lynch, D. R.
Affiliations
  • University of Pennsylvania (US)
  • Children's Hospital of Philadelphia (US)
Corresponding author
Lynch, David R.
Venue
The Neuroscientist
Published
2005-02
Volume
11
Issue
1
Pages
37-49
ISSN
  • 1073-8584 (ISSN-L)
  • 1089-4098
OpenAlex
W2121402661
Cited by
372
References
97
Citations by year
2026: 4 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 16 · 2020: 10 · 2019: 17 · 2018: 15 · 2017: 10 · 2016: 15 · 2015: 20 · 2014: 24 · 2013: 30 · 2012: 15
FWCI
2.32
Type
journal article
Language
en
Open access
closed
Locations
  • The Neuroscientist (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Mental Health (T32MH014654, T32 MH 14654)
  • National Institute of Neurological Disorders and Stroke (NS 45986)
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 › Receptor Mechanisms and Signaling
Keywords
NMDA receptor, NMDA receptor subtypes, excitotoxicity, neurological disorders, mitochondrial dysfunction, calcium-dependent enzyme, MAPK signaling, neuronal cell death
MeSH terms
Animals, Central Nervous System, Humans, Synaptic Transmission, Neurotoxins, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Cell Death, Neurodegenerative Diseases, Protein Subunits

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