Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1783720312885477376
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
work_keys_str_mv AT behltapan thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT kaurishnoor thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT sehgalaayush thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT singhsukhbir thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT bhatiasaurabh thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT alharrasiahmed thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT zengingokhan thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT bumbuadriangheorghe thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT androniecioarafelicialiana thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT nechiforaureliacristina thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT giteadaniela thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT bungaualexaflorina thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT tomamirelamarioara thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT bungausimonagabriela thefootprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT behltapan footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT kaurishnoor footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT sehgalaayush footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT singhsukhbir footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT bhatiasaurabh footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT alharrasiahmed footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT zengingokhan footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT bumbuadriangheorghe footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT androniecioarafelicialiana footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT nechiforaureliacristina footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT giteadaniela footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT bungaualexaflorina footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT tomamirelamarioara footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications
AT bungausimonagabriela footprintofkynureninepathwayinneurodegenerationjanusfacedroleinparkinsonsdisorderandtherapeuticimplications