Glutamate is the main excitatory neurotransmitter in the CNS. During normal signal transmission between nerve cells (neurons), glutamate is released from certain nerve cells. Glutamate binds to glutamate receptors on adjacent neurons and thus produces transmission of signals in the CNS. The glutamate signal is controlled precisely as glutamate is transported back by specific transport proteins (glutamate transporters) in support (glial) and nerve cells. Under certain circumstances, such as loss of glutamate uptake proteins or uncontrolled glutamate release, however, high glutamate concentrations can occur in the synaptic gap, which trigger a neurotoxic process. Apart from a disturbance of glutamate transport, changes in the receptors for glutamate are regarded as a possible factor in the nerve cell damage (Fig. 1).

The glutamate receptors represent cellular channels, whose activation leads to an influx of sodium and calcium ions into the nerve cell. A disturbance of the receptor structure or an excessive concentration of glutamate outside the neurons now leads to an excessive influx of calcium into the nerve cell, which results in damage to the neuron. It is well known that high calcium concentrations can attack cell structures by activating other injury pathways and can destroy the cell.