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Title: The kynurenine pathway and neurodegenerative disease
Authors: Maddison, Daniel C.
Giorgini, Flaviano
First Published: 12-Mar-2015
Publisher: Elsevier
Citation: Seminars in Cell and Developmental Biology, April 2015, 40, pp. 134-141
Abstract: Neuroactive metabolites of the kynurenine pathway (KP) of tryptophan degradation have been closely linked to the pathogenesis of several neurodegenerative diseases. Tryptophan is an essential amino acid required for protein synthesis, and in higher eukaryotes is also converted into the key neurotransmitters serotonin and tryptamine. However, in mammals >95% of tryptophan is metabolized through the KP, ultimately leading to the production of nicotinamide adenosine dinucleotide (NAD(+)). A number of the pathway metabolites are neuroactive; e.g. can modulate activity of several glutamate receptors and generate/scavenge free radicals. Imbalances in absolute and relative levels of KP metabolites have been strongly associated with neurodegenerative disorders including Huntington's, Alzheimer's, and Parkinson's diseases. The KP has also been implicated in the pathogenesis of other brain disorders (e.g. schizophrenia, bipolar disorder), as well as several cancers and autoimmune disorders such as HIV. Pharmacological and genetic manipulation of the KP has been shown to ameliorate neurodegenerative phenotypes in a number of model organisms, suggesting that it could prove to be a viable target for the treatment of such diseases. Here, we provide an overview of the KP, its role in neurodegeneration and the current strategies for therapeutic targeting of the pathway.
DOI Link: 10.1016/j.semcdb.2015.03.002
ISSN: 1084-9521
eISSN: 1096-3634
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015 Elsevier. Archived in accordance with the publishers open access policy available on Sherpa romeo.
Description: The file associated with this record is under embargo for 12 months from date of first publication.
Appears in Collections:Published Articles, Dept. of Genetics

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