Excitotoxicity is the pathological process by which neurons are damaged and killed by the overactivations of receptors for the excitatory neurotransmitter glutamate, such as the NMDA receptor and AMPA receptor.

Excitotoxins like NMDA and kainic acid which bind to these receptors, as well as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium ions to enter the cell.

Ca++ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain.

These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA. Excitotoxicity may be involved in stroke, traumatic brain injury and neurodegenerative diseases of the central nervous system (CNS) such as Multiple sclerosis, Alzheimer's disease, Amyotrophic lateral sclerosis (ALS), Fibromyalgia, Parkinson's disease, and Huntington's disease.

Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia and status epilepticus..

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