Related Experiment Video

Updated: Aug 5, 2026

Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models
10:46

Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models

Published on: May 3, 2017

Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death

R Sattler1, M Tymianski

  • 1Johns Hopkins University School of Medicine, Howard Hughes Medical Institute, Department of Neuroscience, Baltimore MD 21209, USA. r_sattler_99@yahoo.com

Molecular Neurobiology
|February 8, 2002
PubMed

Insights

Excitotoxicity, a key process in neuronal cell death, involves excessive glutamate release activating receptors. This review details the molecular mechanisms of N-methyl-D-aspartate (NMDA) and AMPA/kainate receptor-mediated excitotoxicity.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pathology

Background:

  • Excitotoxicity is a major mechanism of neuronal cell death implicated in central nervous system (CNS) diseases like ischemia, trauma, and neurodegeneration.
  • It is characterized by excessive synaptic glutamate release, leading to overactivation of postsynaptic glutamate receptors.
  • While multiple glutamate receptor subtypes are involved, N-methyl-D-aspartate (NMDA) receptors are considered primary mediators due to their high calcium permeability.

Purpose of the Study:

  • To review the molecular mechanisms underlying excitotoxic neuronal cell death.
  • To elucidate the roles of NMDA receptors and AMPA/kainate receptors in excitotoxicity.
  • To summarize the calcium-dependent nature of glutamate toxicity.

Main Methods:

  • Literature review of studies on excitotoxicity.
  • Analysis of molecular pathways involved in glutamate receptor activation.
  • Synthesis of findings on calcium influx and neuronal death.

Main Results:

  • NMDA receptors, due to high Ca2+ permeability, play a significant role in excitotoxic cell death.
  • AMPA and kainate receptors also contribute critically to excitotoxic neuronal death.
  • The molecular basis of excitotoxicity is largely dependent on intracellular calcium (Ca2+) levels.

Conclusions:

  • Understanding NMDA and AMPA/kainate receptor-mediated excitotoxicity is crucial for developing treatments for CNS disorders.
  • Calcium-dependent mechanisms are central to excitotoxic neuronal death.
  • Further research into these pathways may reveal therapeutic targets for neuroprotection.

More Related Videos

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons10:36

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons

Published on: November 6, 2017

Examination of Anatomical Features of Retinal Ganglion Cells Under N-methyl-D-aspartic Acid (NMDA)-induced Excitotoxicity07:11

Examination of Anatomical Features of Retinal Ganglion Cells Under N-methyl-D-aspartic Acid (NMDA)-induced Excitotoxicity

Published on: September 19, 2025

Related Concept Videos

Fusion of Secretory Vesicles with the Plasma Membrane01:26

Fusion of Secretory Vesicles with the Plasma Membrane

Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
Excitatory and Inhibitory Effects of Neurotransmitters01:29

Excitatory and Inhibitory Effects of Neurotransmitters

When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of specific...
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...