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IDO level increase in Kynurenine Pathway Contributes to the Development of Alzheimer's Disease

Published: 09 December 2022 Publication History

Abstract

Tryptophan is crucial to many functions of the body. Research has shown that its involvement in the Kynurenine pathway (KP) also plays a role in the development of various neurodegenerative diseases (ND). As one of the upstream enzymes in KP, Indoleamine 2,3-dioxygenase (IDO) controls the production of several critical downstream metabolites. Some of these metabolites, such as kynurenic acid (KYNA), possess neuroprotective properties, while some other, such as quinolinic acid (QUIN) are neurotoxic. Hence, the balance between these species is closely linked to the pathogenesis of NDs. Interesting, a positive association has also been found between the level of IDO and the level of amyloid peptide Aβ1-42 involved in Alzheimer's disease. Therefore, this experiment aims to investigate the mechanistic link between increases in levels of IDO and beta-amyloid production. We hypothesize that an increase in IDO level caused by systemic inflammation promotes the generation of key markers of AD by causing an imbalance in levels of tryptophan metabolites, specifically by shifting towards production of neurotoxic metabolite (QUIN) over neuroprotective species (KYNA).

References

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"IDO1 Indoleamine 2,3-Dioxygenase 1 [Homo Sapiens (Human)] - Gene - NCBI". Ncbi.Nlm.Nih.Gov, 2022, https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermTo Search=3620.
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          cover image ACM Other conferences
          ISAIMS '22: Proceedings of the 3rd International Symposium on Artificial Intelligence for Medicine Sciences
          October 2022
          594 pages
          ISBN:9781450398442
          DOI:10.1145/3570773
          Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

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          Published: 09 December 2022

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