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Ostapiuk A, Urbanska EM. Kynurenic acid in neurodegenerative disorders-unique neuroprotection or double-edged sword?. CNS Neurosci Ther. 2021;28(1):19-35doi: 10.1111/cns.13768.
Ostapiuk, A., & Urbanska, E. M. (2022). Kynurenic acid in neurodegenerative disorders-unique neuroprotection or double-edged sword?. CNS neuroscience & therapeutics, 28(1), 19-35. https://doi.org/10.1111/cns.13768
Ostapiuk, Aleksandra, and Urbanska, Ewa M. "Kynurenic acid in neurodegenerative disorders-unique neuroprotection or double-edged sword?." CNS neuroscience & therapeutics vol. 28,1 (2022): 19-35. doi: https://doi.org/10.1111/cns.13768
Ostapiuk A, Urbanska EM. Kynurenic acid in neurodegenerative disorders-unique neuroprotection or double-edged sword?. CNS Neurosci Ther. 2022 Jan;28(1):19-35. doi: 10.1111/cns.13768. Epub 2021 Dec 03. PMID: 34862742.
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CNS Neurosci Ther. 2022 Jan;28(1):19-35. doi: 10.1111/cns.13768. Epub 2021 Dec 03.

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

CNS neuroscience & therapeutics

Aleksandra Ostapiuk, Ewa M Urbanska

Affiliations

  1. Laboratory of Cellular and Molecular Pharmacology, Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Lublin, Poland.

PMID: 34862742 DOI: 10.1111/cns.13768

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.

© 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Keywords: Alzheimer's disease; Huntington's disease; N-methyl-D-aspartate; Parkinson's disease; mitochondrial toxin; neurodegeneration

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