Excitotoxic and excitoprotective mechanisms

@article{Mattson2007ExcitotoxicAE,
  title={Excitotoxic and excitoprotective mechanisms},
  author={Mark P. Mattson},
  journal={NeuroMolecular Medicine},
  year={2007},
  volume={3},
  pages={65-94}
}
  • M. Mattson
  • Published 2007
  • Biology, Chemistry
  • NeuroMolecular Medicine
Activation of glutamate receptors can trigger the death of neurons and some types of glial cells, particularly when the cells are coincidentally subjected to adverse conditions such as reduced levels of oxygen or glucose, increased levels of oxidative stress, exposure to toxins or other pathogenic agents, or a disease-causing genetic mutation. Such excitotoxic cell death involves excessive calcium influx and release from internal organelles, oxyradical production, and engagement of programmed… 

Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders.

  • M. Mattson
  • Biology
    Antioxidants & redox signaling
  • 2006
Emerging findings suggest that the resistance of neurons to death during aging can be enhanced by modifications of diet and lifestyle.

Cell Death Mechanisms of Neurodegeneration.

There are common mechanisms shared by genetically or pathologically distinct neurodegenerative diseases, such as excitotoxicity, mitochondrial deficits and oxidative stress, protein misfolding and translational dysfunction, autophagy and microglia activation, that may lead to final execution of cell death through similar pathways.

Neuroprotection through stimulation of mitochondrial antioxidant protein expression.

Evidence indicates that mitochondria are a target of the cytoprotective gene expression induced by Nrf2 and that this pathway can increase resistance to redox-regulated opening of the permeability transition pore, which may constitute a powerful mechanism for both pre-conditioning against neurodegeneration and for post- conditioning against neural cell death associated with acute neurologic injury.

Nicotinamide Prevents NAD+ Depletion and Protects Neurons Against Excitotoxicity and Cerebral Ischemia: NAD+ Consumption by SIRT1 may Endanger Energetically Compromised Neurons

SIRT1 is linked to bioenergetic state and stress responses in neurons, and that under conditions of reduced cellular energy levels SIRT1 enzyme activity may consume sufficient NAD+ to nullify any cell survival-promoting effects of its deacetylase action on protein substrates.

Neuronal changes under excitotoxic conditions: the role of 26S proteasome

The chymotrypsin-like activity of the proteasome decreased by 50% when determined 4 h after excitotoxic stimulation with glutamate, and these results were correlated with a decrease in cell survival, suggesting that is may be impaired in brain ischemia.
...

References

SHOWING 1-10 OF 290 REFERENCES

Excitotoxicity and mitochondria.

The mitochondrial generation of superoxide anions is enhanced during glutamate exposure and a working hypothesis is that DCD may be caused by oxidative damage to calcium extrusion pathways at the plasma membrane.

Caspase-Mediated Apoptosis in Neuronal Excitotoxicity Triggered by Nitric Oxide

In CGC, NO donors elicit apoptosis by a mechanism involving excitotoxic mediators, Ca2+ overload, and subsequent activation of caspases, which differs from direct NO toxicity in some other neuronal populations and does not involve PARP activation.

Neuroprotective Signal Transduction: Relevance to Stroke

  • M. Mattson
  • Biology
    Neuroscience & Biobehavioral Reviews
  • 1997

Evidence for Synaptic Apoptosis

The data demonstrate that apoptotic biochemical cascades can be activated locally in synapses and dendrites and suggest a role for such local apoptotic signals in synapse loss and neuronal death in neurodegenerative disorders that involve excessive activation of glutamate receptors.

Caspase pathways, neuronal apoptosis, and CNS injury.

Evidence is provided for the potential therapeutic use of caspase inhibitors in the setting of acute and chronic CNS injury, and for their role in mediating cell death in chronic neurodegenerative conditions such as Alzheimer's disease, Huntington’s disease, and amyotrophic lateral sclerosis.

The role of excitotoxicity in neurodegenerative disease: implications for therapy.

  • A. Doble
  • Biology, Medicine
    Pharmacology & therapeutics
  • 1999

Glutamate induced cell death: apoptosis or necrosis?

Calpain inhibitors prevent nitric oxide-triggered excitotoxic apoptosis

It is suggested that block of calpains blunts NO-triggered neuronal apoptosis by stopping the cascade downstream of primary autocrine excitotoxic events.

Caspase-Mediated Suppression of Glutamate (AMPA) Receptor Channel Activity in Hippocampal Neurons in Response to DNA Damage Promotes Apoptosis and Prevents Necrosis: Implications for Neurological Side Effects of Cancer Therapy and Neurodegenerative Disorders

Caspase-mediated suppression of AMPA currents may allow neurons with damaged DNA to withdraw their participation in excitatory circuits and undergo apoptosis, thereby avoiding widespread necrosis and have important implications for treatment of patients with cancer and neurodegenerative disorders.
...