Glutamate can have an indirect toxic effect by depleting intracellular glutathione. The cystine-glutamate antiporter transports cystine into the cell and is driven by the movement of glutamate out of the cell. Cystine and glutamate compete to bind to the antiporter so increased levels of glutamate reduce the amount of cystine entering the cell. Cystine is a precursor for intracellular glutathione which has multiple functions within the cell, notably protection to the cell from oxidative damage and a direct effect on K+ conductance which …show more content…
Thus motor neurone groups that tend to be spared in ALS, oculomotor (III) nucleus, express a lower density of NMDA receptor binding sites and an increased density of AMPA binding sites compared with vulnerable motor neuron groups. This indicates differences in normal glutamate neurotransmission in spared and vulnerable motor neurone groups. Recent studies have found a specific, non-competitive NMDA receptor blocker, memantin, was able to delay the disease progression and prolong life span in mSOD1 mouse model through both subcutaneous and oral administrations [81][82].