Kynurenines in chronic neurodegenerative disorders: future therapeutic strategies.
Parkinson's, Alzheimer's and Huntington's diseases are chronic neurodegenerative disorders of a progressive nature which lead to a considerable deterioration of the quality of life. Their pathomechanisms display some common features, including an imbalance of the tryptophan metabolism. Alterations in the concentrations of neuroactive kynurenines can be accompanied by devastating excitotoxic injuries and metabolic disturbances. From therapeutic considerations, possibilities that come into account include increasing the neuroprotective effect of kynurenic acid, or decreasing the levels of neurotoxic 3-hydroxy-L-kynurenine and quinolinic acid. The experimental data indicate that neuroprotection can be achieved by both alternatives, suggesting opportunities for further drug development in this field.
Zádori
D
D
Department of Neurology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary.
Klivényi
P
P
Vámos
E
E
Fülöp
F
F
Toldi
J
J
Vécsei
L
L
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007736:Kynurenic Acid / Q000819:agonists / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009243:NAD / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D018698:Glutamic Acid; D007736:Kynurenic Acid; D009243:NAD; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017378:Quinolinic Acid; D014364:Tryptophan