BIOENERGETICS AND GLUTAMATE EXCITOTOXICITY

Bioenergetic defects and abnormalities in glutamate neurotransmission have both been proposed to play important roles in neurological diseas es of varying chronology, etiology and pathology. Recent experimental evidence suggests an intimate relationship between these two systems. Metabolic inhibition predisposes neurons to glutamate-mediated ''excit otoxic'' damage. The exact mechanism of this increased susceptibility is yet to be defined, but may involve, singly or in combination, decre ased voltage-dependent Mg2+ blockade of the N-methyl-D-aspartate (NMDA ) subtype of glutamate receptor, abnormalities in cellular Ca2+ homeos tasis, or elevated production of reactive oxygen species. It is believ ed that enhancement of excitotoxicity by impaired metabolism may be a ubiquitous mechanism of neuronal death in neurological disease. Furthe r elucidation of the exact mechanism of this enhancement may lead to t he discovery of new targets for therapeutic intervention. Copyright (C ) 1996 Elsevier Science Ltd