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

Author

Stone, Trevor W. and Darlington, L. Gail

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-recognised 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 an unique position to mediate the effects of environmental factors on cognition and behaviour. Targetting 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.

Published
2013

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

Author

Stone TW and Darlington LG

Subjects
Animals, Central Nervous System drug effects, Central Nervous System enzymology, Central Nervous System metabolism, Cognition Disorders enzymology, Cognition Disorders metabolism, Drugs, Investigational therapeutic use, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase antagonists & inhibitors, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Kynurenine 3-Monooxygenase antagonists & inhibitors, Kynurenine 3-Monooxygenase metabolism, Nerve Tissue Proteins antagonists & inhibitors, Nerve Tissue Proteins metabolism, Neurodegenerative Diseases enzymology, Neurodegenerative Diseases metabolism, Neurons drug effects, Neurons enzymology, Neurons metabolism, Transaminases antagonists & inhibitors, Transaminases metabolism, Cognition Disorders drug therapy, Enzyme Inhibitors therapeutic use, Kynurenine metabolism, Molecular Targeted Therapy, Neurodegenerative Diseases drug therapy, Nootropic Agents therapeutic use
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., (© 2013 The British Pharmacological Society.)

Published
2013
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