Genetic alterations affecting the genes encoding the enzymes of the kynurenine pathway and their association with human diseases

Fanni A. Boros, Zsuzsanna Bohár, L. Vécsei

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

Tryptophan is metabolized primarily via the kynurenine pathway (KP), which involves several enzymes, including indoleamine 2,3-dioxygenase, tryptophan 2,3 dioxygenase (TDO), kynurenine aminotransferases (KATs), kynurenine monooxygenase (KMO) etc. The majority of metabolites are neuroactive: some of them, such as kynurenic acid, show neuroprotective effects, while others contribute to free radical production, leading to neurodegeneration. Imbalance of the pathway is assumed to contribute to the development of several neurodegenerative diseases, psychiatric disorders, migraine and multiple sclerosis. Our aim was to summarize published data on genetic alterations of enzymes involved in the KP leading to disturbances of the pathway that can be related to different diseases. To achieve this, a PubMed literature search was performed for publications on genetic alterations of the KP enzymes upto April 2017. Several genetic alterations of the KP have been identified and have been proposed to be associated with diseases. Here we must emphasize that despite the large number of recognized genetic alterations, the number of firmly established causal relations with specific diseases is still small. The realization of this by those interested in the field is very important and finding such connections should be a major focus of related research. Polymorphisms of the genes encoding the enzymes of the KP have been associated with autism, multiple sclerosis and schizophrenia, and were shown to affect the immune response of patients with bacterial meningitis, just to mention a few. To our knowledge, this is the first comprehensive review of the genetic alterations of the KP enzymes. We believe that the identification of genetic alterations underlying diseases has great value regarding both treatment and diagnostics in precision medicine, as this work can promote the understanding of pathological mechanisms, and might facilitate medicinal chemistry approaches to substitute missing components or correct the disturbed metabolite balance of KP.

Original languageEnglish
Pages (from-to)32-45
Number of pages14
JournalMutation Research - Reviews in Mutation Research
Volume776
DOIs
Publication statusPublished - Apr 1 2018

Fingerprint

Kynurenine
Enzymes
Genes
kynurenine-oxoglutarate transaminase
Multiple Sclerosis
Tryptophan Oxygenase
Indoleamine-Pyrrole 2,3,-Dioxygenase
Kynurenic Acid
Precision Medicine
Bacterial Meningitides
Pharmaceutical Chemistry
Neuroprotective Agents
Autistic Disorder
Mixed Function Oxygenases
Migraine Disorders
PubMed
Tryptophan
Neurodegenerative Diseases
Free Radicals
Psychiatry

Keywords

  • Genetic alterations
  • Kynurenines
  • Metabolic disturbances
  • Metabolic enzymes
  • Polymorphism
  • Tryptophan metabolism

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

Genetic alterations affecting the genes encoding the enzymes of the kynurenine pathway and their association with human diseases. / Boros, Fanni A.; Bohár, Zsuzsanna; Vécsei, L.

In: Mutation Research - Reviews in Mutation Research, Vol. 776, 01.04.2018, p. 32-45.

Research output: Contribution to journalReview article

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