title: Involvement of the kynurenine pathway in the pathogenesis of Parkinson's disease.
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.
authors.affiliation: Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
authors.forename: Chai K
authors.initials: CK
authors.lastname: Lim
authors.affiliation: Clinical & Experimental Neuroscience, Institute of Biomedical Research of Murcia (IMIB), Institute of Aging Research, School of Medicine, University of Murcia, 30100 Murcia, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Fernández-Gomez
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.affiliation: Clinical & Experimental Neuroscience, Institute of Biomedical Research of Murcia (IMIB), Institute of Aging Research, School of Medicine, University of Murcia, 30100 Murcia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Estrada
authors.affiliation: Clinical & Experimental Neuroscience, Institute of Biomedical Research of Murcia (IMIB), Institute of Aging Research, School of Medicine, University of Murcia, 30100 Murcia, Spain; Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
authors.forename: Cristina
authors.initials: C
authors.lastname: Costa
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
authors.forename: Silvia
authors.initials: S
authors.lastname: Costa
authors.affiliation: ImmuSmol, Pessac, France.
authors.forename: Alban
authors.initials: A
authors.lastname: Bessede
authors.affiliation: Clinical & Experimental Neuroscience, Institute of Biomedical Research of Murcia (IMIB), Institute of Aging Research, School of Medicine, University of Murcia, 30100 Murcia, Spain.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Fernandez-Villalba
authors.affiliation: Vascular Immunology Unit, Dept of Pathology, Sydney Medical School, The University of Sydney, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Zinger
authors.affiliation: Clinical & Experimental Neuroscience, Institute of Biomedical Research of Murcia (IMIB), Institute of Aging Research, School of Medicine, University of Murcia, 30100 Murcia, Spain. Electronic address: mtherrer@um.es.
authors.forename: Maria Trinidad
authors.initials: MT
authors.lastname: Herrero
authors.affiliation: Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia; Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St Vincent's Centre for Applied Medical Research, Sydney, Australia. Electronic address: gilles.guillemin@mq.edu.au.
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
mesh_terms: D000818:Animals; D006801:Humans; D007737:Kynurenine / Q000276:immunology / Q000378:metabolism*; D010300:Parkinson Disease / Q000276:immunology / Q000378:metabolism*
chemical_list: D007737:Kynurenine