Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism
Worldwide, 50 million people suffer from dementia, a group of symptoms affecting cognitive and social functions, progressing severely enough to interfere with daily life. Alzheimer’s disease (AD) accounts for most of the dementia cases. Pathological and clinical findings have led to propos...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/3/564 |
| _version_ | 1818506319286501376 |
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| author | Masaru Tanaka Zsuzsanna Bohár László Vécsei |
| author_facet | Masaru Tanaka Zsuzsanna Bohár László Vécsei |
| author_sort | Masaru Tanaka |
| collection | DOAJ |
| description | Worldwide, 50 million people suffer from dementia, a group of symptoms affecting cognitive and social functions, progressing severely enough to interfere with daily life. Alzheimer’s disease (AD) accounts for most of the dementia cases. Pathological and clinical findings have led to proposing several hypotheses of AD pathogenesis, finding a presence of positive feedback loops and additionally observing the disturbance of a branch of tryptophan metabolism, the kynurenine (KYN) pathway. Either causative or resultant of dementia, elevated levels of neurotoxic KYN metabolites are observed, potentially upregulating multiple feedback loops of AD pathogenesis. Memantine is an N-methyl-D-aspartate glutamatergic receptor (NMDAR) antagonist, which belongs to one of only two classes of medications approved for clinical use, but other NMDAR modulators have been explored so far in vain. An endogenous KYN pathway metabolite, kynurenic acid (KYNA), likewise inhibits the excitotoxic NMDAR. Besides its anti-excitotoxicity, KYNA is a multitarget compound that triggers anti-inflammatory and antioxidant activities. Modifying the KYNA level is a potential multitarget strategy to normalize the disturbed KYN pathway and thus to alleviate juxtaposing AD pathogeneses. In this review, the maintenance of KYN metabolism by modifying the level of KYNA is proposed and discussed in search for a novel lead compound against the progression of dementia. |
| first_indexed | 2024-12-10T22:02:57Z |
| format | Article |
| id | doaj.art-1cde6f824add4002982076f02661bb9e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-10T22:02:57Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-1cde6f824add4002982076f02661bb9e2022-12-22T01:31:51ZengMDPI AGMolecules1420-30492020-01-0125356410.3390/molecules25030564molecules25030564Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine MetabolismMasaru Tanaka0Zsuzsanna Bohár1László Vécsei2MTA-SZTE, Neuroscience Research Group, Semmelweis u. 6, H-6725 Szeged, HungaryMTA-SZTE, Neuroscience Research Group, Semmelweis u. 6, H-6725 Szeged, HungaryMTA-SZTE, Neuroscience Research Group, Semmelweis u. 6, H-6725 Szeged, HungaryWorldwide, 50 million people suffer from dementia, a group of symptoms affecting cognitive and social functions, progressing severely enough to interfere with daily life. Alzheimer’s disease (AD) accounts for most of the dementia cases. Pathological and clinical findings have led to proposing several hypotheses of AD pathogenesis, finding a presence of positive feedback loops and additionally observing the disturbance of a branch of tryptophan metabolism, the kynurenine (KYN) pathway. Either causative or resultant of dementia, elevated levels of neurotoxic KYN metabolites are observed, potentially upregulating multiple feedback loops of AD pathogenesis. Memantine is an N-methyl-D-aspartate glutamatergic receptor (NMDAR) antagonist, which belongs to one of only two classes of medications approved for clinical use, but other NMDAR modulators have been explored so far in vain. An endogenous KYN pathway metabolite, kynurenic acid (KYNA), likewise inhibits the excitotoxic NMDAR. Besides its anti-excitotoxicity, KYNA is a multitarget compound that triggers anti-inflammatory and antioxidant activities. Modifying the KYNA level is a potential multitarget strategy to normalize the disturbed KYN pathway and thus to alleviate juxtaposing AD pathogeneses. In this review, the maintenance of KYN metabolism by modifying the level of KYNA is proposed and discussed in search for a novel lead compound against the progression of dementia.https://www.mdpi.com/1420-3049/25/3/564dementiaalzheimer’s diseasekynurenineskynurenic acidneuroprotective agentsantioxidant moleculesmultitarget agents |
| spellingShingle | Masaru Tanaka Zsuzsanna Bohár László Vécsei Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism Molecules dementia alzheimer’s disease kynurenines kynurenic acid neuroprotective agents antioxidant molecules multitarget agents |
| title | Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism |
| title_full | Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism |
| title_fullStr | Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism |
| title_full_unstemmed | Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism |
| title_short | Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism |
| title_sort | are kynurenines accomplices or principal villains in dementia maintenance of kynurenine metabolism |
| topic | dementia alzheimer’s disease kynurenines kynurenic acid neuroprotective agents antioxidant molecules multitarget agents |
| url | https://www.mdpi.com/1420-3049/25/3/564 |
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