Kynurenines in the CNS: from endogenous obscurity to therapeutic importance

@article{Stone2001KynureninesIT,
  title={Kynurenines in the CNS: from endogenous obscurity to therapeutic importance},
  author={Trevor W. Stone},
  journal={Progress in Neurobiology},
  year={2001},
  volume={64},
  pages={185-218}
}
  • T. Stone
  • Published 1 June 2001
  • Biology, Medicine
  • Progress in Neurobiology
5 Kynurenines in the Brain: Preclinical and Clinical Studies, Therapeutic Considerations
TLDR
The discovery of the importance of kynurenines in brain function under physiological and pathologic conditions has led to the identification of potential new drug targets exploiting the therapeutic potential of the pathway.
Kynurenines in neurodegenerative disorders: therapeutic consideration.
The kynurenine pathway is a major route for the conversion of tryptophane to NAD and NADP (Figure 1), leading to production of a number of biologically active molecules with neuroactive properties.
Involvement of kynurenines in Huntington’s disease and stroke-induced brain damage
TLDR
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 and conclude thatkynurenine pathway activation closely reflects cognitive function, and may play a significant role in cognitive ability.
Kynurenines, Parkinson's disease and other neurodegenerative disorders: preclinical and clinical studies.
TLDR
It seems hopeful to use kynurenine derivatives or enzyme inhibitors to ensure an increased kynurenic acid concentration in the central nervous system to exert its neuroprotective effects binding at the excitatory glutamate receptors, in particular the NMDA receptors.
L-kynurenine: Metabolism and mechanism of neuroprotection
TLDR
This review summarizes the main steps of the kynurenine pathway under normal conditions, discusses the metabolic disturbances and changes in this pathway in certain neurodegenerative disorders, and introduces the therapeutic applications of this pathway.
Tryptophan Metabolites and Brain Disorders
TLDR
Tryptophan is metabolised primarily along the kynurenine pathway, of which two components are now known to have marked effects on neurons in the central nervous system, raising the possibility that interference with their actions or synthesis could lead to new forms of pharmacotherapy for these conditions.
Kynurenine and its metabolites in Alzheimer's disease patients.
TLDR
Examination of peripheral KP in patients with Alzheimer type dementia proves activation of peripheral kynurenine pathway in this type of dementia and offers Novel therapeutic opportunities, with the development of new compounds as a promising perspective for brain neuroprotection.
Does kynurenic acid act on nicotinic receptors? An assessment of the evidence
  • T. Stone
  • Biology
    Journal of neurochemistry
  • 2019
TLDR
There is no confirmed, reliable evidence for an antagonist activity of kynurenic acid at nicotinic receptors, and since there is overwhelming evidence for kynurenate acting at ionotropic glutamate receptors, especially NMDAR glutamate and glycine sites, results with kynUREnic acid should be interpreted only in terms of these confirmed sites of action.
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References

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Development and therapeutic potential of kynurenic acid and kynurenine derivatives for neuroprotection.
  • T. Stone
  • Biology, Chemistry
    Trends in pharmacological sciences
  • 2000
Kynurenine metabolism in Alzheimer's disease
TLDR
The present data indicate an elevated kynurenine metabolism in AD brain and a marked increase of KYNA in the caudate nucleus and putamen may compensate the hyperactivity of the striato-frontal loop in AD brains.
Inhibitors of the kynurenine pathway.
  • T. Stone
  • Biology, Chemistry
    European journal of medicinal chemistry
  • 2000
TLDR
It is proving possible to interfere directly with the kynurenine pathway to block the synthesis of quinolinic acid and promote the formation of kynurenic acid, which yields neuroprotectant and anticonvulsant compounds.
Neuropharmacology of quinolinic and kynurenic acids.
  • T. Stone
  • Biology
    Pharmacological reviews
  • 1993
TLDR
Whatever the specific nature of their physiological roles, the presence of an endogenous selective agonist and antagonist acting at NMDA receptors must continue to present exciting possibilities for understanding the pathological basis of several CNS disorders as well as developing new therapeutic approaches.
Dysfunction of brain kynurenic acid metabolism in Huntington's disease: focus on kynurenine aminotransferases
Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex
Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease.
TLDR
It is concluded that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease.
Role of kynurenines in the neurotoxic actions of kainic acid
TLDR
Results indicate that inhibition of the kynurenine pathway offers protection against kainate‐induced damage, and one possible mechanism for the protection is that an increased production of quinolinic acid in the brain, possibly from glial cells and macrophages activated by the initial kainic acid insult, normally contributes to the local activation of NMDA receptors and thus to kainates‐induced cerebral insults.
Effects of immune activation on quinolinic acid and neuroactive kynurenines in the mouse
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