Disorders of glutamate metabolism and neurological dysfunction

Annual Review of Medicine
S B Prusiner

Abstract

Disorders of glutamate metabolism are associated with profound alteration of CNS function. Although the precise biochemical mechanisms responsible for nervous system dysfunction in most of these disorders are unknown, it can be concluded that biochemical aberrations in the metabolism of glutamate usually result in malfunction of the CNS. As with most disorders of amino acid metabolism that are associated with brain dysfunction, the molecular mechanisms underlying pathogenesis of these disorders remain obscure. Why do some biochemically affected individuals remain free of significant neurological involvement? The explanation that the accumulation of a specific metabolite is responsible for the pathogenesis of a disease process does not answer this and may frequently prove to be incorrect. More complete descriptions of these disorders of glutamate metabolism and their attendant neurological dysfunction will be required before any firm linkage between the biochemical defects and the clinical manifestations of the disease processes can be established. In addition, a much greater knowledge of the control mechanisms regulating glutamate metabolism in the CNS will be needed before the complexities of these disorders can be fully under...Continue Reading

Citations

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