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...

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Veröffentlicht in:International journal of molecular sciences 2021-06, Vol.22 (13), p.6737
Hauptverfasser: 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
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Sprache:eng
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Zusammenfassung: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22136737