Dynamic Changes in Metabolites of the Kynurenine Pathwayinalzheimer’Sdisease,Andhuntington’Sdisease: A Systematic Review of Pre-Clinical Studies Publisher



F Ahmadi FARZANEH ; S Behzadi SALEH ; K Aghazadehhabashi KOMEIL ; K Eyvani KIMIA ; A Fatehi ANITA ; M Alipour MILAD ; F Sodeifian FATEMEH ; Fr Khajeh Faraz RAHMANI ; Am Azaribakhsh Amir MAHDI ; A Nazerian AMIRHOSSEIN
Source: Caspian Journal of Neurological Sciences Published:2024

Abstract

Background: Alterations in the kynurenine pathway (KP) metabolite can contribute to the pathogenesis and progression of many psychiatric and neurodegenerative illnesses, including Alzheimer disease (AD) and Huntington disease (HD), primarily through neuroinflammatory pathways and generating neurotoxic metabolites. Objectives: This systematic review highlights the evidence obtained by in vivo animal studies on alterations in KP metabolites and enzymes in AD and HD. Materials & Methods: We searched PubMed, Scopus, Web of Science, and EMBASE databases from the beginning of 2000 to January 2024 and included English-language in vivo articles comparing levels of KP metabolites or enzymes in rats or mice AD or HD models with controls. Results: A total of 19 studies, comprising 93 experimental and 95 control animals, were included. In AD models compared to controls, the following changes were reported: higher levels of tryptophan (TRP) in blood; higher kynurenine (KYN) levels in the cortex, hippocampus, hypothalamus, and prefrontal cortex; higher quinolinic acid (QUIN) levels in the hippocampus and cerebrum; higher indoleamine 2,3-dioxygenases levels in the cerebrum, prefrontal cortex, and hippocampus; and a higher KYN/TRP ratio in the hippocampus, cortex, and cerebellum. Reports on HD models compared to controls showed higher 3-hydroxykynurenine levels in the striatum and cortex and lowered TRP levels in the striatum. Conclusion: According to the primary outcomes, KP alterations may lead to the progression of AD and HD. These two diseases can also change the KP pathway factors. Here, we highlighted that changes in the KP metabolites and enzyme levels can help diagnose and treat these diseases. © 2025 Elsevier B.V., All rights reserved.