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Cited by 142Tryptophan and brain disordersNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments

Kynurenic acid in neurodegenerative disorders-unique neuroprotection or double-edged sword?

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Ostapiuk, Aleksandra, Urbanska, Ewa M.·2022·CNS Neuroscience & Therapeutics
DOI 10.1111/cns.13768PMC PMC8673711
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Abstract

Aims: The family of kynurenine pathway (KP) metabolites includes compounds produced along two arms of the path and acting in clearly opposite ways. The equilibrium between neurotoxic kynurenines, such as 3‐hydroxykynurenine (3‐HK) or quinolinic acid (QUIN), and neuroprotective kynurenic acid (KYNA) profoundly impacts the function and survival of neurons. This comprehensive review summarizes accumulated evidence on the role of KYNA in Alzheimer's, Parkinson's and Huntington's diseases, and discusses future directions of potential pharmacological manipulations aimed to modulate brain KYNA. Discussion: The synthesis of specific KP metabolites is tightly regulated and may considerably vary under physiological and pathological conditions. Experimental data consistently imply that shift of the KP to neurotoxic branch producing 3‐HK and QUIN formation, with a relative or absolute deficiency of KYNA, is an important factor contributing to neurodegeneration. Targeting specific brain regions to maintain adequate KYNA levels seems vital; however, it requires the development of precise pharmacological tools, allowing to avoid the potential cognitive adverse effects. Conclusions: Boosting KYNA levels, through interference with the KP enzymes or through application of prodrugs/analogs with high bioavailability and potency, is a promising clinical approach. The use of KYNA, alone or in combination with other compounds precisely influencing specific populations of neurons, is awaiting to become a significant therapy for neurodegenerative disorders.

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Authors
Ostapiuk, A., & Urbanska, E. M.
Affiliations
  • Medical University of Lublin (PL)
  • Laboratory of Cellular and Molecular Pharmacology Department of Experimental and Clinical Pharmacology Medical University of Lublin Lublin Poland
ORCID
Venue
CNS Neuroscience & Therapeutics
Publisher
Wiley
Published
2021-12-03
Volume
28
Issue
1
Pages
19-35
ISSN
  • 1755-5930 (ISSN-L)
  • 1755-5949
DOI
10.1111/cns.13768
PMC
PMC8673711
OpenAlex
W3215089600
Cited by
142
References
4
Citations by year
2026: 33 · 2025: 34 · 2024: 33 · 2023: 31 · 2022: 10 · 2021: 1
FWCI
1.77
Type
journal article
Language
en
Open access
Licence
Locations
  • CNS Neuroscience & Therapeutics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
kynurenic acid, kynurenine pathway, neurodegeneration, neuroprotection, 3-hydroxykynurenine, quinolinic acid, Alzheimer's disease, Parkinson's disease, Huntington's disease, neurotoxicity, prodrugs, cognitive side effects
MeSH terms
Alzheimer Disease, Animals, Brain, Humans, Huntington Disease, Kynurenic Acid, Kynurenine, Neurons, Parkinson Disease, Signal Transduction, Quinolinic Acid, Excitatory Amino Acid Antagonists, Neuroprotective Agents, Neurodegenerative Diseases

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