Amyotrophic Lateral Sclerosis and Glutamate — Too Much of a Good Thing?

The dicarboxylic amino acid glutamate is not only an essential amino acid but also a signaling substance, serving as a workhorse neurotransmitter at many excitatory synapses in the central nervous system. Glutamate is present in millimolar concentrations throughout the brain and spinal cord, mostly in the presynaptic terminals of excitatory neurons, and it exerts a powerful neuroexcitant action on virtually all central neurons. Normally, glutamatergic transmission is a closely controlled process; the release and cellular reuptake of glutamate are carefully regulated, so that neurons are exposed to it only briefly and at low levels appropriate for synaptic neurotransmission or neurotrophic . . .