Tryptophan, adenosine, neurodegeneration and neuroprotection.
This review summarises the potential contributions of two groups of compounds to cerebral dysfunction and damage in metabolic disease. The kynurenines are oxidised metabolites of tryptophan, the kynurenine pathway being the major route for tryptophan catabolism in most tissues. The pathway includes quinolinic acid -- an agonist at N-methyl-D-aspartate (NMDA) receptors, kynurenic acid -- an antagonist at glutamate and nicotinic receptors, and other redox active compounds that are able to generate free radicals under many physiological and pathological conditions. The pathway is activated in immune-competent cells, including glia in the central nervous system, and may contribute substantially to delayed neuronal damage following an infarct or metabolic insult. Adenosine is an ubiquitous purine that can protect neurons by suppressing excitatory neurotransmitter release, reducing calcium fluxes and inhibiting NMDA receptors. The extent of brain injury is critically dependent on the balance between the two opposing forces of kynurenines and purines.
Stone
T W
TW
Institute of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow, Scotland, UK. t.w.stone@bio.gla.ac.uk
Forrest
C M
CM
Mackay
G M
GM
Stoy
N
N
Darlington
L G
LG
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007737:Kynurenine / Q000502:physiology*; D009243:NAD / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology*; D018696:Neuroprotective Agents; D018384:Oxidative Stress; D017378:Quinolinic Acid / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D018047:Receptors, Purinergic P1 / Q000502:physiology; D014364:Tryptophan / Q000378:metabolism*
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; D009243:NAD; D007737:Kynurenine; D014364:Tryptophan; D017378:Quinolinic Acid; D000241:Adenosine
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