EXCITOTOXICITY AND NEURODEGENERATIVE DISEASES

Glutamate is an excitatory neurotransmitter in the mammalian central n ervous system and a neurotoxin (excitotoxin) that has the potential to destroy neurones by activation of ionotropic receptors. In contrast t o the well documented role of glutamate in the pathogenesis of neurona l degeneration resulting from hypoxia/ischaemia, hypoglycaemia, status epilepticus and trauma, it has been difficult to establish a link bet ween the excitotoxicity and neuronal death that occur in chronic neuro degenerative disorders. Impairment of energy metabolism has been shown to increase neuronal vulnerability to glutamate. The cause of this ph enomenon lies in the attenuation of the Mg2+ blockade of the N-methyl- D-aspartate receptors that leads to persistent activation of these rec eptors by physiologic extracellular glutamate concentrations. The conc ept of increased neuronal vulnerability to excitotoxic injury establis hes a link between slow neuronal degeneration and excitotoxicity and s uggests that glutamate antagonists may prove beneficial in the treatme nt of chronic neurodegenerative diseases that have been resistant to t herapy.