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Towards an understanding of the role of glutamate in neurodegenerative disorders: energy metabolism and neuropathology

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Abstract

It is thought that impairment, of energy metabolism that results in deterioration 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 toxins, such as aminooxyacetic acid, 1-methyl-4-phenylpyridinium, malonic acid and 3-nitropropionic acid, suggest that such processes may indeed be involved in neurotoxicity. Striatal and nigral degeneration induced by mitochondrial toxins in rodents resembles the neuropathology seen in humans suffering from Huntington's or Parkinson's disease, and can be prevented either by decortication or by NMDA receptor antagonists. Such experimental observations suggest that glutamate may be involved in neuronal death leading to neurodegenerative disorders in humans. If so, glutamate antagonists may offer a therapeutic approach for retarding the progression of these disabling disorders.

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  1. Research Laboratories of Schering AG, Müllerstr. 178, D-13342, Berlin, (Germany)

    L. Turski

  2. Department of Clinical Toxicology, Institute of Agricultural, Medicine, Jaczewskiego 2, P.O. Box 185, PL-20-950, Lublin, (Poland)

    W. A. Turski

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Turski, L., Turski, W.A. Towards an understanding of the role of glutamate in neurodegenerative disorders: energy metabolism and neuropathology. Experientia 49, 1064–1072 (1993). https://doi.org/10.1007/BF01929915

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