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The footprint of kynurenine pathway in neurodegeneration: Janus-faced role in parkinson’s disorder and therapeutic implications

International Journal of Molecular Sciences · Temmuz 2021

Makale Bilgileri

DergiInternational Journal of Molecular Sciences
Yayın TarihiTemmuz 2021
Cilt / Sayfa22
Erişim🔓 Açık Erişim
Özet 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.

Yazarlar (14)

1
Tapan Behl
2
Ishnoor Kaur
3
Aayush Sehgal
4
Sukhbir Singh
5
Saurabh Bhatia
6
Ahmed Al-Harrasi
7
Gokhan Zengin
ORCID: 0000-0001-6548-7823
8
Adrian Gheorghe Bumbu
9
Felicia Liana Andronie-Cioara
10
Aurelia Cristina Nechifor
11
Daniela Gitea
12
Alexa Florina Bungau
13
Mirela Marioara Toma
14
Simona Bungau

Anahtar Kelimeler

Janus-faced role Kynurenic acid Kynurenine pathway Neuroprotective Neurotoxic Parkinson’s disease Quinolinic acid

Kurumlar

AUH-Gurugram
Gurugram India
Chitkara University, Punjab
Rajpura India
Selçuk Üniversitesi
Selçuklu Turkey
Universitatea din Oradea, Facultatea de Medicina
Oradea Romania
University of Nizwa
Nizwa Oman
University of Oradea
Oradea Romania
University Politehnica of Bucharest
Bucharest Romania

Metrikler

23
Atıf
14
Yazar
7
Anahtar Kelime

Sistemimizdeki Yazarlar