The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) is unknown, but several observations suggest that glutamate could participate in selective motor neuron degeneration. Extracellular levels of gluta- \ mate are elevated in ALS. Synaptic concentrations of gluta- \. mate are regulated by high-affinity glutamate transport, and defects in glutamate transport have also been observed in ALS tissue. Three sodium-dependent glutamate transporters have now been identified: a neuronal transporter EAAC1, and two astroglial transporters GLT-1 and GLAST. The defect in glutamate transport in ALS appears to be relatively specific for the GLT-1 subtype. The role of chronic excess glutamate and glutamate transporter loss has been investigated in experimental paradigms, where it was found that excitotoxicity could account for selective motor neuron degeneration. These culture paradigms have demonstrated that motor neurons are sensitive to glutamate toxicity via non-NMDA receptors and that various agents (e.g., antioxidants, glutamate release inhibitors, non-NMDA receptor antagonists) can be neuroprotective. These experimental studies will provide a basis for understanding the primary and secondary rote of glutamate in motor neuron death and will provide important insight into possible therapeutic interventions. & 1996 Wiley-Liss, Inc.
|Original language||English (US)|
|Number of pages||12|
|State||Published - Dec 1 1995|
- Combination therapy
- Glutamate transport
ASJC Scopus subject areas
- Neuropsychology and Physiological Psychology