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The kynurenine pathway implicated in patient delirium: possible indications for indoleamine 2,3 dioxygenase inhibitors
Tryptophan (Trp) metabolism plays a central role in sleep, mood, and immune system regulation. The kynurenine pathway (KP), which is regulated by the enzymes tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3 dioxygenase (IDO), which catalyze the conversion of Trp to kynurenine (Kyn), facilitates...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Clinical Investigation
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9843043/ https://www.ncbi.nlm.nih.gov/pubmed/36647830 http://dx.doi.org/10.1172/JCI164577 |
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author | Heimberger, Amy B. Lukas, Rimas V. |
author_facet | Heimberger, Amy B. Lukas, Rimas V. |
author_sort | Heimberger, Amy B. |
collection | PubMed |
description | Tryptophan (Trp) metabolism plays a central role in sleep, mood, and immune system regulation. The kynurenine pathway (KP), which is regulated by the enzymes tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3 dioxygenase (IDO), which catalyze the conversion of Trp to kynurenine (Kyn), facilitates immune regulation and influences neurocognition. Notably, Kyn metabolites bind the N-methyl-d-aspartate receptor (NMDAR), essential for memory encoding, and in turn, cognition. Aberrant NMDAR activity through agonist binding influences excitability and cell death. In this issue of the JCI, Watne and authors demonstrate that KP pathway end products were elevated in the serum and the cerebrospinal fluid (CSF) of subjects with delirium. This observation provides insight regarding the basis of a variety of commonly observed clinical conditions including sundowning, abnormal sleep-wake cycles in hospitalized patients, neurodegenerative cognitive impairment, radiation-induced cognitive impairment, neurocognitive symptomatology related to COVID-19, and clinical outcomes observed in patients with CNS tumors, such as gliomas. |
format | Online Article Text |
id | pubmed-9843043 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-98430432023-01-20 The kynurenine pathway implicated in patient delirium: possible indications for indoleamine 2,3 dioxygenase inhibitors Heimberger, Amy B. Lukas, Rimas V. J Clin Invest Commentary Tryptophan (Trp) metabolism plays a central role in sleep, mood, and immune system regulation. The kynurenine pathway (KP), which is regulated by the enzymes tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3 dioxygenase (IDO), which catalyze the conversion of Trp to kynurenine (Kyn), facilitates immune regulation and influences neurocognition. Notably, Kyn metabolites bind the N-methyl-d-aspartate receptor (NMDAR), essential for memory encoding, and in turn, cognition. Aberrant NMDAR activity through agonist binding influences excitability and cell death. In this issue of the JCI, Watne and authors demonstrate that KP pathway end products were elevated in the serum and the cerebrospinal fluid (CSF) of subjects with delirium. This observation provides insight regarding the basis of a variety of commonly observed clinical conditions including sundowning, abnormal sleep-wake cycles in hospitalized patients, neurodegenerative cognitive impairment, radiation-induced cognitive impairment, neurocognitive symptomatology related to COVID-19, and clinical outcomes observed in patients with CNS tumors, such as gliomas. American Society for Clinical Investigation 2023-01-17 /pmc/articles/PMC9843043/ /pubmed/36647830 http://dx.doi.org/10.1172/JCI164577 Text en © 2023 Heimberger et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Commentary Heimberger, Amy B. Lukas, Rimas V. The kynurenine pathway implicated in patient delirium: possible indications for indoleamine 2,3 dioxygenase inhibitors |
title | The kynurenine pathway implicated in patient delirium: possible indications for indoleamine 2,3 dioxygenase inhibitors |
title_full | The kynurenine pathway implicated in patient delirium: possible indications for indoleamine 2,3 dioxygenase inhibitors |
title_fullStr | The kynurenine pathway implicated in patient delirium: possible indications for indoleamine 2,3 dioxygenase inhibitors |
title_full_unstemmed | The kynurenine pathway implicated in patient delirium: possible indications for indoleamine 2,3 dioxygenase inhibitors |
title_short | The kynurenine pathway implicated in patient delirium: possible indications for indoleamine 2,3 dioxygenase inhibitors |
title_sort | kynurenine pathway implicated in patient delirium: possible indications for indoleamine 2,3 dioxygenase inhibitors |
topic | Commentary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9843043/ https://www.ncbi.nlm.nih.gov/pubmed/36647830 http://dx.doi.org/10.1172/JCI164577 |
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