Mechanisms of excitotoxicity in neurologic diseases

@article{Beal1992MechanismsOE,
  title={Mechanisms of excitotoxicity in neurologic diseases},
  author={M. Flint Beal},
  journal={The FASEB Journal},
  year={1992},
  volume={6},
  pages={3338 - 3344}
}
  • M. Beal
  • Published 1 December 1992
  • Biology, Medicine
  • The FASEB Journal
Excitotoxicity refers to neuronal cell death caused by activation of excitatory amino acid receptors. A substantial body of evidence has implicated excitotoxicity as a mechanism of cell death in both acute and chronic neurologic diseases. A major recent advance has been the successful cloning and expression of the N‐methyl‐d‐aspartate (NMDA), non‐NMDA, and metabotropic glutamate receptors. The cellular mechanisms responsible for cell death after activation of these receptors are still being… 
Excitotoxicity: An Organized Crime at The Cellular Level
TLDR
This review explores the current views on the neurobiological and clinical aspects of excitotoxicity, presenting this process as a complex organized crime at the cellular level.
Role of Metabotropic Glutamate Receptors in Neuronal Degeneration
TLDR
Although the role of glutamate-induced neurotoxicity in chronic neurodegenerative disease remains unclear, compelling evidence suggests that ischemia-triggered neuronal damage is largely attributed to excessive and persistent activation of glutamate receptors.
Selective activation of central subtypes of the nicotinic acetylcholine receptor has opposite effects on neonatal excitotoxic brain injuries
  • V. Laudenbach, F. Medja, P. Gressens
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2002
TLDR
It is found that nicotine is neuroprotective in vivo, in a murine model of neonatal excitotoxic brain injury, and in vitro, in primary cultures of cortical neurons.
Slow excitotoxicity in Alzheimer's disease.
Progress is being made in identifying possible pathogenic factors and novel genes in the development of Alzheimer's disease (AD). Many of these could contribute to 'slow excitotoxicity', defined as
Peripheral Biomarkers of Excitotoxicity in Neurological Diseases
TLDR
In this chapter, findings regarding excitotoxicity biomarkers in peripheral ex vivo cells, such as platelets and fi broblasts, will be described focusing on different neurological diseases, together with a review of the available literature.
The metabolic response to excitotoxicity – lessons from single-cell imaging
TLDR
Some of the knowledge of the neuronal metabolic response to excitotoxicity gained from in vitro single-cell imaging is reviewed, including calcium and ATP dynamics and their effects on mitochondrial function, along with the contribution of glucose metabolism, oxidative stress and additional neuroprotective signalling mechanisms.
Investigating the neuroprotective potential of short-term 5-HT7 receptor activation against neuronal excitotoxicity
TLDR
After extensive characterization of the cell line, it was determined that differentiated HT22 cells were susceptible to NMDA-induced excitotoxicity, and this study aimed to determine if such a neuroprotective pathway could be active with short-term application of a 5-HT7 receptor agonist.
Effect of glutamate on lysosomal membrane permeabilization in primary cultured cortical neurons
TLDR
LMP was significantly alleviated by treatment with the antioxidant N-Acetyl-L-cysteine, indicating that LMP involvement in early glutamate excitotoxicity may be mediated partly by ROS rather than calpain activation.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 87 REFERENCES
Alternative excitotoxic hypotheses
TLDR
This work suggests two modified forms of the excitotoxic hypothesis in which specific populations of neurons become more vulnerable to excitOToxic insult either by possessing abnormal excitatory amino acid receptor subtypes or being afflicted by any disease process that impairs cellular energy metabolism or otherwise decreases neuronal membrane potential.
Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?
  • M. Beal
  • Biology
    Annals of neurology
  • 1992
TLDR
If defective mitochondrial energy metabolism plays a role in cell death in neurodegenerative disorders, potential therapeutic strategies would be to use excitatory amino acid antagonists or agents to bypass bioenergetic defects.
Abusive stimulation of excitatory amino acid receptors: a strategy to limit neurotoxicity
TLDR
The intracellular sequelae of physiological and pathological glutamate receptor activation are described and potential targets for receptor abuse‐dependent antagonists (RADAs) are suggested.
Activation of the metabotropic glutamate receptor attenuates N-methyl-D-aspartate neurotoxicity in cortical cultures.
TLDR
Concomitant activation of the ACPD receptor may serve as a protective mechanism against neurotoxicity that could be produced by brief intense NMDA receptor activation during normal or abnormal brain function.
Mechanisms underlying initiation of excitotoxicity associated with metabolic inhibition.
TLDR
Temporal studies of "severe" metabolic inhibition and the rise in excitatory amino acids demonstrated that the early acute pathology was mediated exclusively by the NMDA receptor and occurred before elevation in excited amino acids.
Aminooxyacetic Acid Results in Excitotoxin Lesions by a Novel Indirect Mechanism
TLDR
The results raise the possibility that a regional impairment of intracellular energy metabolism may secondarily result in excitotoxic neuronal death in chronic neurodegenerative illnesses, such as Huntington's disease.
Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death
  • S. Rothman
  • Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1984
TLDR
Results provide convincing evidence that the synaptic release of excitatory transmitter mediates the death of anoxic neurons, and suggests new strategies that may be effective in preventing the devastating insults produced by cerebral hypoxia and ischemia in man.
...
1
2
3
4
5
...