The kynurenine pathway as a therapeutic target in cognitive and neurodegenerative disorders

Br J Pharmacol. 2013 Jul;169(6):1211-27. doi: 10.1111/bph.12230.

Abstract

Understanding the neurochemical basis for cognitive function is one of the major goals of neuroscience, with a potential impact on the diagnosis, prevention and treatment of a range of psychiatric and neurological disorders. In this review, the focus will be on a biochemical pathway that remains under-recognized in its implications for brain function, even though it can be responsible for moderating the activity of two neurotransmitters fundamentally involved in cognition - glutamate and acetylcholine. Since this pathway - the kynurenine pathway of tryptophan metabolism - is induced by immunological activation and stress, it also stands in a unique position to mediate the effects of environmental factors on cognition and behaviour. Targeting the pathway for new drug development could, therefore, be of value not only for the treatment of existing psychiatric conditions, but also for preventing the development of cognitive disorders in response to environmental pressures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Central Nervous System / drug effects
  • Central Nervous System / enzymology
  • Central Nervous System / metabolism
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / enzymology
  • Cognition Disorders / metabolism
  • Drugs, Investigational / therapeutic use
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Kynurenine / metabolism*
  • Kynurenine 3-Monooxygenase / antagonists & inhibitors
  • Kynurenine 3-Monooxygenase / metabolism
  • Molecular Targeted Therapy*
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / enzymology
  • Neurodegenerative Diseases / metabolism
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / metabolism
  • Nootropic Agents / therapeutic use*
  • Transaminases / antagonists & inhibitors
  • Transaminases / metabolism

Substances

  • Drugs, Investigational
  • Enzyme Inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Nerve Tissue Proteins
  • Nootropic Agents
  • Kynurenine
  • Kynurenine 3-Monooxygenase
  • Transaminases
  • kynurenine-oxoglutarate transaminase