TOWARDS AN UNDERSTANDING OF THE ROLE OF GLUTAMATE IN NEURODEGENERATIVE DISORDERS - ENERGY-METABOLISM AND NEUROPATHOLOGY

It is thought that impairment of energy metabolism that results in det erioration of membrane function, leading to loss of the Mg2+ block on NMDA receptors, and allowing persistent activation of these receptors by glutamate, might be a cause of neuronal death in neurodegenerative disorders. Studies in rodents using mitochondrial respiratory chain to xins, such as aminooxyacetic acid, 1-methyl-4-phenylpyridinium, maloni c acid and 3-nitropropionic acid, suggest that such processes may inde ed be involved in neurotoxicity. Striatal and nigral degeneration indu ced by mitochondrial toxins in rodents resembles the neuropathology se en in humans suffering from Huntington's or Parkinson's disease, and c an be prevented either by decortication or by NMDA receptor antagonist s. Such experimental observations suggest that glutamate may be involv ed in neuronal death leading to neurodegenerative disorders in humans. If so, glutamate antagonists may offer a therapeutic approach for ret arding the progression of these disabling disorders.