Excitotoxin

Excitotoxin refers to any substance that overactivates excitatory amino acid receptors in the brain, most notably NMDA, AMPA, and kainate receptors. This overactivation causes excessive calcium influx into neurons, triggering a cascade of intracellular events that can damage cellular structures and lead to cell death.

Endogenous excitotoxins include the neurotransmitter glutamate, aspartate, and metabolic byproducts such as quinolinic acid. Exogenous excitotoxins include domoic acid, produced by certain algae and responsible for amnesic shellfish poisoning, and kainic acid, which is used in research. The concept of excitotoxicity has been central to explanations of neuronal injury in conditions such as stroke and traumatic brain injury, where excessive glutamatergic signaling is implicated in the extent of tissue damage.

Clinical relevance of excitotoxicity lies in its proposed contribution to both acute and chronic brain injury. In acute settings, limiting excitotoxic cascades is a therapeutic goal; in chronic neurodegenerative diseases, excitotoxic processes are considered one of several interacting pathways. Developing effective interventions has been challenging, and no universally effective anti-excitotoxic therapy is in routine clinical use.

Dietary and public discussions sometimes describe certain food ingredients as excitotoxins, especially monosodium glutamate (MSG). Regulatory agencies generally consider MSG safe for the general population at typical intake levels, though some individuals report sensitivity. The term remains a topic in popular discourse, but robust evidence for widespread harm from normal dietary consumption is not established.