Dynamic changes in metabolites of the kynurenine pathway in Alzheimer's disease, Parkinson's disease, and Huntington's disease: A systematic Review and meta-analysis

被引：45

作者：

Fathi, Mobina ^{[1
]}

Vakili, Kimia ^{[1
]}

Yaghoobpoor, Shirin ^{[1
]}

Tavasol, Arian ^{[1
]}

Jazi, Kimia ^{[2
]}

Hajibeygi, Ramtin ^{[3
]}

Shool, Sina ^{[4
]}

Sodeifian, Fatemeh ^{[1
]}

Klegeris, Andis ^{[5
]}

McElhinney, Alyssa ^{[5
]}

Tavirani, Mostafa Rezaei ^{[6
]}

Sayehmiri, Fatemeh ^{[1
]}

机构：

[1] Shahid Beheshti Univ Med Sci, Student Res Comm, Fac Med, Tehran, Iran

[2] Med Univ Qom, Student Res Comm, Fac Med, Qom, Iran

[3] Islamic Azad Univ, Fac Med, Dept Neurol, Tehran Med Sci, Tehran, Iran

[4] Shahid Beheshti Univ Med Sci, Fac Med, Tehran, Iran

[5] Univ British Columbia Okanagan Campus, Fac Sci, Dept Biol, Kelowna, BC, Canada

[6] Shahid Beheshti Univ Med Sci, Fac Paramed Sci, Prote Res Ctr, Tehran, Iran

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷

关键词：

alzheimer's disease; parkinson's disease; huntington's disease; kynurenine (KYN); tryptophan; kynurenic acid; anthranilic acid; CEREBROSPINAL-FLUID; TRYPTOPHAN DEGRADATION; OXIDATIVE STRESS; ACID LEVELS; 5-HYDROXYINDOLEACETIC ACID; HOMOVANILLIC-ACID; QUINOLINIC ACID; BRAIN; 3-HYDROXYKYNURENINE; SEROTONIN;

D O I：

10.3389/fimmu.2022.997240

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: Tryptophan (TRP) is an essential amino acid that must be provided in the diet. The kynurenine pathway (KP) is the main route of TRP catabolism into nicotinamide adenosine dinucleotide (NAD(+)), and metabolites of this pathway may have protective or degenerative effects on the nervous system. Thus, the KP may be involved in neurodegenerative diseases. Objectives: The purpose of this systematic review and meta-analysis is to assess the changes in KP metabolites such as TRP, kynurenine (KYN), kynurenic acid (KYNA), Anthranilic acid (AA), 3-hydroxykynurenine (3-HK), 5-Hydroxyindoleacetic acid (5-HIAA), and 3-Hydroxyanthranilic acid (3-HANA) in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) patients compared to the control group. Methods: We conducted a literature search using PubMed/Medline, Scopus, Google Scholar, Web of Science, and EMBASE electronic databases to find articles published up to 2022. Studies measuring TRP, KYN, KYNA, AA, 3-HK, 5-HIAA, 3-HANA in AD, PD, or HD patients and controls were identified. Standardized mean differences (SMDs) were used to determine the differences in the levels of the KP metabolites between the two groups. Results: A total of 30 studies compromising 689 patients and 774 controls were included in our meta-analysis. Our results showed that the blood levels of TRP was significantly lower in the AD (SMD=-0.68, 95% CI=-0.97 to -0.40, p=0.000, I2 = 41.8%, k=8, n=382), PD (SMD=-0.77, 95% CI=-1.24 to -0.30, p=0.001, I2 = 74.9%, k=4, n=352), and HD (SMD=-0.90, 95% CI=-1.71 to -0.10, p=0.028, I2 = 91.0%, k=5, n=369) patients compared to the controls. Moreover, the CSF levels of 3-HK in AD patients (p=0.020) and the blood levels of KYN in HD patients (p=0.020) were lower compared with controls. Conclusion: Overall, the findings of this meta-analysis support the hypothesis that the alterations in the KP may be involved in the pathogenesis of AD, PD, and HD. However, additional research is needed to show whether other KP metabolites also vary in AD, PD, and HD patients. So, the metabolites of KP can be used for better diagnosing these diseases.

引用

页数：23

共 108 条

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