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The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson’s Disorder and Therapeutic Implications
Progressive degeneration of neurons and aggravation of dopaminergic neurons in the substantia nigra pars compacta results in the loss of dopamine in the brain of Parkinson’s disease (PD) patients. Numerous therapies, exhibiting transient efficacy have been developed; however, they are mostly accompa...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268239/ https://www.ncbi.nlm.nih.gov/pubmed/34201647 http://dx.doi.org/10.3390/ijms22136737 |
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author | Behl, Tapan Kaur, Ishnoor Sehgal, Aayush Singh, Sukhbir Bhatia, Saurabh Al-Harrasi, Ahmed Zengin, Gokhan Bumbu, Adrian Gheorghe Andronie-Cioara, Felicia Liana Nechifor, Aurelia Cristina Gitea, Daniela Bungau, Alexa Florina Toma, Mirela Marioara Bungau, Simona Gabriela |
author_facet | Behl, Tapan Kaur, Ishnoor Sehgal, Aayush Singh, Sukhbir Bhatia, Saurabh Al-Harrasi, Ahmed Zengin, Gokhan Bumbu, Adrian Gheorghe Andronie-Cioara, Felicia Liana Nechifor, Aurelia Cristina Gitea, Daniela Bungau, Alexa Florina Toma, Mirela Marioara Bungau, Simona Gabriela |
author_sort | Behl, Tapan |
collection | PubMed |
description | Progressive degeneration of neurons and aggravation of dopaminergic neurons in the substantia nigra pars compacta results in the loss of dopamine in the brain of Parkinson’s disease (PD) patients. Numerous therapies, exhibiting transient efficacy have been developed; however, they are mostly accompanied by side effects and limited reliability, therefore instigating the need to develop novel optimistic treatment targets. Significant therapeutic targets have been identified, namely: chaperones, protein Abelson, glucocerebrosidase-1, calcium, neuromelanin, ubiquitin-proteasome system, neuroinflammation, mitochondrial dysfunction, and the kynurenine pathway (KP). The role of KP and its metabolites and enzymes in PD, namely quinolinic acid (QUIN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranillic acid (3-HAA), kunurenine-3-monooxygenase (KMO), etc. has been reported. The neurotoxic QUIN, N-methyl-D-aspartate (NMDA) receptor agonist, and neuroprotective KYNA—which antagonizes QUIN actions—primarily justify the Janus-faced role of KP in PD. Moreover, KP has been reported to play a biomarker role in PD detection. Therefore, the authors detail the neurotoxic, neuroprotective, and immunomodulatory neuroactive components, alongside the upstream and downstream metabolic pathways of KP, forming a basis for a therapeutic paradigm of the disease while recognizing KP as a potential biomarker in PD, thus facilitating the development of a suitable target in PD management. |
format | Online Article Text |
id | pubmed-8268239 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82682392021-07-10 The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson’s Disorder and Therapeutic Implications Behl, Tapan Kaur, Ishnoor Sehgal, Aayush Singh, Sukhbir Bhatia, Saurabh Al-Harrasi, Ahmed Zengin, Gokhan Bumbu, Adrian Gheorghe Andronie-Cioara, Felicia Liana Nechifor, Aurelia Cristina Gitea, Daniela Bungau, Alexa Florina Toma, Mirela Marioara Bungau, Simona Gabriela Int J Mol Sci Review Progressive degeneration of neurons and aggravation of dopaminergic neurons in the substantia nigra pars compacta results in the loss of dopamine in the brain of Parkinson’s disease (PD) patients. Numerous therapies, exhibiting transient efficacy have been developed; however, they are mostly accompanied by side effects and limited reliability, therefore instigating the need to develop novel optimistic treatment targets. Significant therapeutic targets have been identified, namely: chaperones, protein Abelson, glucocerebrosidase-1, calcium, neuromelanin, ubiquitin-proteasome system, neuroinflammation, mitochondrial dysfunction, and the kynurenine pathway (KP). The role of KP and its metabolites and enzymes in PD, namely quinolinic acid (QUIN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranillic acid (3-HAA), kunurenine-3-monooxygenase (KMO), etc. has been reported. The neurotoxic QUIN, N-methyl-D-aspartate (NMDA) receptor agonist, and neuroprotective KYNA—which antagonizes QUIN actions—primarily justify the Janus-faced role of KP in PD. Moreover, KP has been reported to play a biomarker role in PD detection. Therefore, the authors detail the neurotoxic, neuroprotective, and immunomodulatory neuroactive components, alongside the upstream and downstream metabolic pathways of KP, forming a basis for a therapeutic paradigm of the disease while recognizing KP as a potential biomarker in PD, thus facilitating the development of a suitable target in PD management. MDPI 2021-06-23 /pmc/articles/PMC8268239/ /pubmed/34201647 http://dx.doi.org/10.3390/ijms22136737 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Behl, Tapan Kaur, Ishnoor Sehgal, Aayush Singh, Sukhbir Bhatia, Saurabh Al-Harrasi, Ahmed Zengin, Gokhan Bumbu, Adrian Gheorghe Andronie-Cioara, Felicia Liana Nechifor, Aurelia Cristina Gitea, Daniela Bungau, Alexa Florina Toma, Mirela Marioara Bungau, Simona Gabriela The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson’s Disorder and Therapeutic Implications |
title | The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson’s Disorder and Therapeutic Implications |
title_full | The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson’s Disorder and Therapeutic Implications |
title_fullStr | The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson’s Disorder and Therapeutic Implications |
title_full_unstemmed | The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson’s Disorder and Therapeutic Implications |
title_short | The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson’s Disorder and Therapeutic Implications |
title_sort | footprint of kynurenine pathway in neurodegeneration: janus-faced role in parkinson’s disorder and therapeutic implications |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268239/ https://www.ncbi.nlm.nih.gov/pubmed/34201647 http://dx.doi.org/10.3390/ijms22136737 |
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