Excitotoxicity
In motor neurons, most glutamate is cleared from the synapse by the glial glutamate transporter, EAAT2 (also known as GLT1). In sporadic ALS, glutamate levels are increased in the CSF, suggesting problems with glutamate handling. Glutamate transport is also markedly reduced, due to loss of EAAT2 (shown by reduced EAAT2 protein levels in mutant SOD1 mouse models) and selective inactivation of EAAT2 by mutant SOD1.