Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism
1
MTA-SZTE, Neuroscience Research Group, Semmelweis u. 6, H-6725 Szeged, Hungary
2
Department of Neurology, Interdisciplinary Excellence Centre, Faculty of Medicine, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
*
Author to whom correspondence should be addressed.
Academic Editor: Simona Rapposelli
Molecules 2020, 25(3), 564; https://doi.org/10.3390/molecules25030564
Received: 18 December 2019
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Revised: 24 January 2020
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Accepted: 25 January 2020
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Published: 28 January 2020
(This article belongs to the Special Issue Neuroprotective Agents to Treat Dementias)
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.
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Keywords:
dementia; Alzheimer’s disease; kynurenines; kynurenic acid; neuroprotective agents; antioxidant molecules; multitarget agents
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MDPI and ACS Style
Tanaka, M.; Bohár, Z.; Vécsei, L. Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism. Molecules 2020, 25, 564. https://doi.org/10.3390/molecules25030564
AMA Style
Tanaka M, Bohár Z, Vécsei L. Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism. Molecules. 2020; 25(3):564. https://doi.org/10.3390/molecules25030564
Chicago/Turabian StyleTanaka, Masaru, Zsuzsanna Bohár, and László Vécsei. 2020. "Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism" Molecules 25, no. 3: 564. https://doi.org/10.3390/molecules25030564
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