Kynurenine pathway in Parkinson's disease-An update

Dhivya Venkatesan; Mahalaxmi Iyer; Arul Narayanasamy; Kamalakannan Siva; Balachandar Vellingiri

doi:10.1016/j.ensci.2020.100270

Kynurenine pathway in Parkinson's disease-An update

eNeurologicalSci. 2020 Sep 10:21:100270. doi: 10.1016/j.ensci.2020.100270. eCollection 2020 Dec.

Authors

Dhivya Venkatesan¹, Mahalaxmi Iyer², Arul Narayanasamy³, Kamalakannan Siva⁴, Balachandar Vellingiri¹

Affiliations

¹ Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
² Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore 641 043, Tamil Nadu, India.
³ Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
⁴ National Centre for Disease Control, Ministry of Health and Family Welfare, Government of India, New Delhi 110054, India.

Abstract

Parkinson's disease (PD) is a complex multi-factorial neurodegenerative disorder where various altered metabolic pathways contribute to the progression of the disease. Tryptophan (TRP) is a major precursor in kynurenine pathway (KP) and it has been discussed in various in vitro studies that the metabolites quinolinic acid (QUIN) causes neurotoxicity and kynurenic acid (KYNA) acts as neuroprotectant respectively. More studies are also focused on the effects of other KP metabolites and its enzymes as it has an association with ageing and PD pathogenesis. Until now, very few studies have targeted the role of genetic mutations in abnormal KP metabolism in adverse conditions of PD. Therefore, the present review gives an updated research studies on KP in connection with PD. Moreover, the review emphasizes on the urge for the development of biomarkers and also this would be an initiative in generating an alternative therapeutic approach for PD.

Keywords: 3-HAA, 3-hydroxyanthranilic acid; 3-HK, 3-hydroxykynurenine; 6-OHDA, 6-hydroxydopamine; AA, anthranilic acid; ACMSD, amino-carboxymuconatesemialdehyde decarboxylase; AD, Alzheimer's disease; ATP, adenosine triphosphate; Ageing; AhR, aryl hydrocarbon receptor; Biomarkers; CNS, central nervous system; CSF, cerebrospinal fluid; DA, dopaminergic; FAM, formamidase; IDO-1, indoleamine-2,3-dioxygenases; IFN-γ, interferon-γ; KATs, kynurenine aminotransferases; KMO, kynurenine −3-monooxygenase; KP, Kynurenine pathway; KYN, kynurenine; KYNA, kynurenic acid; Kynurenine pathway (KP); L-DOPA, L-dopamine; LID, L-DOPA-induced dyskinesia; MPTP, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine; NAD+, nicotinamide adenine dinucleotide; NADPH, nicotinamide adenine dinucleotide phosphate; NFK, N′-formylkynurenine; NMDA, N-methyl-d-aspartate; PA, picolinic acid; PD, Parkinson's disease; Parkinson's disease (PD); QUIN, quinolinic acid; RBCs, red blood cells; SNpc, substantianigra pars compacta; TDO, tryptophan 2,3-dioxygenase; TRP, tryptophan; Therapeutics; XA, xanthurenic acid; ZNS, zonisamide; α-synuclein, αSyn.

Publication types

Review