Excitotoxicity and Glutamate
Although motor neurones carry a message along their length as an electrical signal, the signal is initiated in the neurone by a chemical messenger landing on special receptor molecules on the cell surface. It is believed one of the main causes of damage to motor neurones in MND occurs when the neurone becomes over stimulated by chemicals that cause it to “fire”.
When a neurone carries a signal it does so by allowing the electrical charge across the cell membrane to change. As part of these changes sodium and chloride ions flood in bringing water with them. The changes brought about by these events in a healthy cell firing normally are well managed by many different mechanisms within the cell and no damage is done
The amino acid glutamate is used in the healthy nervous system to initiate a signal within a motor neurone, but in some people affected by MND the normal regulation of glutamate appears to have broken down. In consequence the motor neurones are exposed to an excess of glutamate which causes them to fire repeatedly flooding the cell with sodium, chloride and water, causing the whole neurone to swell with consequent disruption to other cell systems leading to cell death. Other amino acids found in the body are also able to fit onto the glutamate receptors of the motor neurone. Unlike glutamate, which is released relatively quickly, these other chemicals stick firmly to the receptors and can cause the death of motor neurones within a second and a half in experimental conditions by causing them to fire rapidly and repeatedly with similar consequences.
Workers in this area are not only investigating the excitotoxic effects of glutamate on neurones and their receptors but are also investigating the systems which are used to manufacture, transport, store, release and recycle glutamate and related compounds.
