Kynurenines, neurodegeneration and Alzheimer's disease

Zsigmond Tamas Kincses, József Toldi, László Vécsei

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

• Alzheimer's disease. • The kynurenine pathway. - Neuroactive kynurenines. - Enzymes of the kynurenine pathway. • Relations of kynurenines to the pathomechanism of AD. - Altered activation of the kynurenine pathway in AD. - Connection of oxidative stress and kynurenines. - Glutamatergic excitotoxicity. - Inflammation. • A future therapeutic approach: modulating the kynurenine pathway. • Concluding remarks. Alzheimer's disease (AD) is one of the major causes of dementia. The pathogenesis of the disease is not entirely understood, but the amyloid β peptide (Aβ) and the formation of senile plaques seem to play pivotal roles. Oligomerization of the Aβ is thought to trigger a cascade of events, including oxidative stress, glutamate excitotoxicity and inflammation. The kynurenine (KYN) pathway is the major route for the metabolism of the essential amino acid tryptophan. Some of the metabolites of this pathway, such as 3-hydroxykynurenine and quinolinic acid, are known to have neurotoxic properties, whereas others, such as kynurenic acid, are putative neuroprotectants. Among other routes, the KYN pathway has been shown to be involved in AD pathogenesis, and connections to other known mechanisms have also been demonstrated. Oxidative stress, glutamate excitotoxicity and the neuroinflammation involved in AD pathogenesis have been revealed to be connected to the KYN pathway. Intervention at these key steps may serve as the aim of potential therapy.

Original languageEnglish
Pages (from-to)2045-2054
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume14
Issue number8
DOIs
Publication statusPublished - Aug 1 2010

Keywords

  • Alzheimer
  • Glutamate excitotoxicity
  • Kynurenine
  • Neuroinflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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