Assessing and Modulating Kynurenine Pathway Dynamics in Huntington's Disease: Focus on Kynurenine 3-Monooxygenase

Methods Mol Biol. 2018:1780:397-413. doi: 10.1007/978-1-4939-7825-0_18.

Abstract

The link between disturbances in kynurenine pathway (KP) metabolism and Huntington's disease (HD) pathogenesis has been explored for a number of years. Several novel genetic and pharmacological tools have recently been developed to modulate key regulatory steps in the KP such as the reaction catalyzed by the enzyme kynurenine 3-monooxygenase (KMO). This insight has offered new options for exploring the mechanistic link between this metabolic pathway and HD, and provided novel opportunities for the development of candidate drug-like compounds. Here, we present an overview of the field, focusing on some novel approaches for interrogating the pathway experimentally.

Keywords: Huntington’s disease; Kynurenine 3-monooxygenase (KMO); Kynurenine pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology*
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Huntingtin Protein / genetics
  • Huntingtin Protein / metabolism
  • Huntington Disease / drug therapy
  • Huntington Disease / genetics
  • Huntington Disease / pathology*
  • Kynurenine / metabolism*
  • Kynurenine 3-Monooxygenase / antagonists & inhibitors
  • Kynurenine 3-Monooxygenase / metabolism*
  • Male
  • Metabolic Networks and Pathways / drug effects*
  • Metabolic Networks and Pathways / genetics
  • Middle Aged
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Tryptophan / metabolism

Substances

  • Enzyme Inhibitors
  • HTT protein, human
  • Huntingtin Protein
  • Neuroprotective Agents
  • Kynurenine
  • Tryptophan
  • Kynurenine 3-Monooxygenase