Involvement of kynurenines in Huntington's disease and stroke-induced brain damage

Several components of the kynurenine pathway of tryptophan metabolism are now recognised to have actions of profound biological importance. These include the ability to modulate the activation of glutamate and nicotinic receptors, to modify the responsiveness of the immune system to inflammation and infection, and to modify the generation and removal of reactive oxygen species. As each of these factors is being recognised increasingly as contributing to major disorders of the central nervous system (CNS), so the potentially fundamental role of the kynurenine pathway in those disorders is presenting a valuable target both for understanding the progress of those disorders and for developing potential drug treatments. This review will summarise some of the evidence for an important contribution of the kynurenines to Huntington's disease and to stroke damage in the CNS. Together with preliminary evidence from a study of kynurenine metabolites after major surgery, an important conclusion is that kynurenine pathway activation closely reflects cognitive function, and may play a significant role in cognitive ability.