Involvement of the kynurenine pathway in the pathogenesis of Parkinson's disease. (August 2017)

• Record Type: Journal Article
• Authors: Lim, Chai K.; Fernández-Gomez, Francisco J.; Braidy, Nady; Estrada, Cristina; Costa, Cristina; Costa, Silvia; Bessede, Alban; Fernandez-Villalba, Emiliano; Zinger, Anna; Herrero, Maria Trinidad; Guillemin, Gilles J.
• Is Part Of: Progress in neurobiology. Volume 155(2017:Aug.)
• Page Start: 76
• Page End: 95
• Publication Date: 2017-08
• Subjects: 3-HK 3-hydroxykynurenine -- 6-OHDA 6-hydroxydopamine -- A Amygdala -- ACMSD 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase -- AD Alzheimer's disease -- AD Anterodorsal nucleus (Thalamus) -- α-syn Alpha-synuclein -- CCL2 Chemokine (CC motif) ligand 2 -- CSF Cerebrospinal fluid -- DA Dopaminergic neurons -- DM Dorsomedial nucleus (Thalamus) -- Glu Glutamatergic pathway -- GPe external Globus Pallidus -- GPi internal Globus Pallidus -- IDO-1 indoleamine 2, 3 dioxygenase -- IL1β Interleukin-1β -- IL8 Interleukin-8 -- INF-γ Interferon-γ -- KAT Kynurenine aminotransferase -- KMO Kynurenine 3-monooxygenase -- KP Kynurenine pathway -- KYN Kynurenine -- KYNA Kynurenic acid -- LBs Lewy bodies -- LID (L-DOPA)-induced dyskinesia's -- LPS Lipopolysaccharides -- MPP+ 1-methyl-4-phenylpyridinium -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- NAD+ Nicotinamide adenine dinucleotide -- NF-κB Nuclear factor kappa B -- NMDA N-methyl-d-aspartate -- NMDA-R NMDA Glutamatergic receptor -- PD Parkinsońs disease -- PYC Pycnogenol -- QPRT Quinolinate phosphoribosyl transferase -- QUIN Quinolinic acid -- REM Rapid Eye Movement -- RN Reticular Nucleus -- ROS Reactive Oxygen Species -- SN Substantia Nigra -- SNpc Substantia Nigra, pars compacta -- SNpr Substantia Nigra, pars reticulata -- SOD Superoxide dismutase -- STN Subthalamic Nucleus -- TH Tyrosine Hydroxylase -- TLR Toll-Like Receptor -- TNF-α Tumour Necrosis Factor-alpha -- TRP Tryptophan -- UCP Uncoupling Protein -- VA Ventral Anterior nucleus (Thalamus) -- VL Ventral Lateral nucleus (Thalamus) -- VM Ventral Medial nucleus (Thalamus); Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2015.12.009
• Languages: English
• ISSNs: 0301-0082

Abstract

Highlights: The kynurenine pathway is one of the major regulators of the immune response and is also implicated in the inflammatory and neurotoxic events in Parkinsonism. Kynurenic acid produced by astrocytes confers neuroprotection whereas quinolinic acid, released by activated microglia, can lead to excitotoxicity and amplify the inflammatory response. Abstract: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons and localized neuroinflammation occurring in the midbrain several years before the actual onset of symptoms. Neuroinflammation leads to microglia activation and release of a large number of proinflammatory mediators. The kynurenine pathway (KP) of tryptophan catabolism is one of the major regulators of the immune response and is also likely to be implicated in the inflammatory and neurotoxic events in Parkinsonism. Several neuroactive compounds are produced through the KP that can be either a neurotoxic, neuroprotective or immunomodulator. Among these metabolites kynurenic acid (KYNA), produced by astrocytes, is considered as neuroprotective whereas quinolinic acid (QUIN), released by activated microglia, can activate the N-methyl-d -aspartate (NMDA) receptor-signalling pathway, leading to excitotoxicity and amplify the inflammatory response. Previous studies have shown that NMDA antagonists can ease symptoms and exert a neuroprotective effect in PD both in vivo and in vitro . There are to date several lines of evidence linking some of the KP intermediates and the neuropathogenesis of PD. Moreover, it is likely that some of the KP metabolites could be used as prognostic biomarkers and that pharmacological modulators of the KP enzymes could represent a new therapeutic strategy for PD.