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Journal of Neural Transmission

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01.02.2012 | Basic Neurosciences, Genetics and Immunology - Review article

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

verfasst von: Judit Füvesi, Cecilia Rajda, Krisztina Bencsik, József Toldi, László Vécsei

Erschienen in: Journal of Neural Transmission | Ausgabe 2/2012

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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.

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Titel: The role of kynurenines in the pathomechanism of amyotrophic lateral sclerosis and multiple sclerosis: therapeutic implications
verfasst von: Judit Füvesi
Cecilia Rajda
Krisztina Bencsik
József Toldi
László Vécsei
Publikationsdatum: 01.02.2012
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 2/2012
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-012-0765-3

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

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