The role of kynurenines in the pathomechanism of amyotrophic lateral sclerosis and multiple sclerosis: Therapeutic implications

Judit Füvesi, Cecilia Rajda, Krisztina Bencsik, József Toldi, László Vécsei

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

Tryptophan is one of the essential amino acids, 80% of which is catabolised in the extrahepatic tissues by indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme of the kynurenine pathway. Metabolites along the kynurenine pathway have been implicated to play a role in the pathomechanism of neuroinflammatory and neurodegenerative disorders. Changes in the concentration levels of kynurenines can shift the balance to pathological conditions. The ability to influence the metabolism towards the neuroprotective branch of the kynurenine pathway, i.e. towards kynurenic acid (KYNA) synthesis, may be one option in preventing neurodegenerative diseases. Three potential therapeutic strategies could be feasible to develop drugs to live up to expectations: (1) chemically related drugs with better bioavailability and higher affinity to the binding sites of excitatory receptors; (2) prodrugs of KYNA, which easily cross the blood-brain barrier combined with an inhibitor of organic acid transport for enhancement of the brain KYNA concentration; (3) inhibitors of enzymes of the kynurenine pathway. In this review, we focus on aspects of the pathomechanism and therapeutic possibilities of amyotrophic lateral sclerosis and multiple sclerosis that may be influenced by kynurenines.

Original languageEnglish
Pages (from-to)225-234
Number of pages10
JournalJournal of neural transmission
Volume119
Issue number2
DOIs
Publication statusPublished - Feb 1 2012

Keywords

  • Amyotrophic lateral sclerosis
  • Inflammation
  • Kynurenic acid
  • Multiple sclerosis
  • Neurodegeneration

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Fingerprint Dive into the research topics of 'The role of kynurenines in the pathomechanism of amyotrophic lateral sclerosis and multiple sclerosis: Therapeutic implications'. Together they form a unique fingerprint.

  • Cite this