The DOI matches its Crossref record; 270 of the 270 references it cites were found in a registry or an index.
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.
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“previous studies showing that quinolinic acid (QA), a QUIN precursor, contributes to neuroinflammation and is implicated in various neurodegenerative diseases [55,56,57].”
In the citing paper
“By contrast, quinolinic acid, released by microglia, can activate the NMDA receptor-signaling pathway, leading to excitotoxicity and increasing the inflammatory response.”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Lim C. K. et al., 2017
In the citing paper
“Recently, the kinurenic pathway (KP) has been implicated in the inflammatory and neurotoxic processes in PD.”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Lim C. K. et al., 2017
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Cites
1 retracted
Braidy, N., Brew, B. J., Inestrosa, N. C., Chung, R. S., Sachdev, P. S., & Guillemin, G. J. (2014) · Metabolic Brain Disease · doi:10.1007/s11011-014-9557-9 · Cited by 19
Self-citationRetractedStaging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777
Epigenetic modifications and human disease
Portela, A., & Esteller, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1685 · Cited by 2,938
The prevalence of Parkinson's disease: a systematic review and meta-analysis
Pringsheim, T., Jette, N., Frolkis, A., & Steeves, T. D. L. (2014) · Movement Disorders · doi:10.1002/mds.25945 · Cited by 2,188
International Parkinson's Disease Genomics Consortium (IPDGC), Nalls, M. A., Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), Investigator, T. A. J. D., (CHARGE), C. F. H. A. A. R. I. G. E., North American Brain Expression Consortium (NABEC), et al. (2014) · Nature Genetics · doi:10.1038/ng.3043 · Cited by 1,895
MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE
Schapira, A. H. V., Cooper, J. A. D., Dexter, D. T., Jenner, P. G., Clark, J. B., & MARSDEN, C. D. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92366-0 · Cited by 1,757
An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells
Mezrich, J. D., Fechner, J. H., Zhang, X., Johnson, B. P., Burlingham, W. J., & Bradfield, C. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903670 · Cited by 1,674
Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives
Mostafalou, S., & Abdollahi, M. R. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.01.025 · Cited by 1,333
Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid
Beal, M. F., Kowall, N. W., Ellison, D. W., Mazurek, M. F., Swartz, K. J., & Martin, J. B. (1986) · Nature · doi:10.1038/321168a0 · Cited by 1,287
Immune system to brain signaling: Neuropsychopharmacological implications
Capuron, L., & Miller, A. H. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.01.014 · Cited by 1,195
Research works printed but not linked: 11
- Bay-Richter, 2014, A role for inflammatory metabolites as modulators of the glutamate N-methyl-d-aspartate receptor in depression and suicidality, Brain Behav. Immun.
- Behan, 1999, Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl, Br. J. Pharmacol., 128, 1754, 10.1038/sj.bjp.0702940 · DOI · Paper page
- Chen, 2009, Kynurenine pathway metabolites in humans: disease and healthy states, Int. J. Trypto. Res., 1, 1
- Goldstein, 2000, 3- Hydroxykynurenine and 3-hydroxyanthranilic acid generate hydrogen peroxide and promote alpha-crystallin cross-linking by metal ion reduction, Biochemistry, 39, 7266, 10.1021/bi992997s · DOI
- Guillemin, 2002, Implications of the kynurenine pathway and quinolinic acid in Alzheimer's disease, Redox Rep., 7, 199, 10.1179/135100002125000550 · DOI
- Guillemin, 2001, Bamyloid peptide 1–42 induces human macrophages to produce the neurotoxin quinolinic acid, J. Neuroimmunol., 118
- Hartai, 2005, Kynurenine metabolism in plasma and in red blood cells in Parkinson's disease, J. Neurol. Sci., 239, 31, 10.1016/j.jns.2005.07.006 · DOI
- Knyihar-Csillik, 2006, Effect of 6-hydroxydopamine treatment on kynurenine aminotransferase-I (KAT-I) immunoreactivity of neurons and glial cells in the rat substantia nigra, Acta Neuropathol., 112, 127, 10.1007/s00401-006-0086-4 · DOI
- Pérez-De La Cruz, 2011, Quinolinic acid, an endogenous molecule combining excitotoxicity, oxidative stress and other toxic mechanisms, FEBS J.
- Schwarcz, 1983, Differential vulnerability of central neurons of the rat to quinolinic acid, Neurosci. Lett., 38, 85, 10.1016/0304-3940(83)90115-5 · DOI · Paper page
- Steiner, 2011, Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: evidence for an immune-modulated glutamatergic neurotransmission?, J. Neuroinflammation, 8, 1, 10.1186/1742-2094-8-94 · DOI · Paper page
Cited by
Sorted by citations
Tryptophan metabolism and gut-brain homeostasis
Roth, W., Zadeh, K., Vekariya, R., Ge, Y., & Mohamadzadeh, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062973 · Cited by 519
The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma.
Ramirez, A. I., de Hoz, R., Salobrar-Garcia, E., Salazar, J. J., Rojas, B., Ajoy, D., López-Cuenca, I., Rojas, P., Triviño, A., & Ramírez, J. M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00214 · Cited by 466
Lovelace, M. D., Varney, B., Sundaram, G., Lennon, M. J., Lim, C. K., Jacobs, K., Guillemin, G. J., & Brew, B. J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.03.024 · Cited by 393
Self-citationMicroglia: Agents of the CNS Pro-Inflammatory Response
Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020) · Cells · doi:10.3390/cells9071717 · Cited by 365
Huang, Y., Zhao, M., Chen, X., Zhang, R., Le, A., Hong, M., Zhang, Y., Jia, L., Zang, W., Jiang, C., et al. (2023) · Aging and disease · doi:10.14336/ad.2022.0916 · Cited by 138
“Related underlying mechanisms include NMDAR activation, ROS production [139], lipid peroxidation, and increased levels of nitric oxide synthase [136].”
BackgroundTryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders
Li, D., Yu, S., Long, Y., Shi, A., Deng, J., Ma, Y., Wen, J., Li, X., Liu, S., Zhang, Y., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.985378 · Cited by 129
Potential roles of gut microbiota and microbial metabolites in Parkinson’s disease
Zheng, S.-Y., Li, H.-X., Xu, R.-C., Miao, W.-T., Dai, M.-Y., Ding, S.-T., & Liu, H.-D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101347 · Cited by 101
Microglia activation contributes to quinolinic acid-induced neuronal excitotoxicity through TNF-α
Feng, W., Wang, Y., Liu, Z.-Q., Zhang, X., Han, R., Miao, Y.-Z., & Qin, Z.-H. (2017) · Apoptosis · doi:10.1007/s10495-017-1363-5 · Cited by 53
Fongsaran, C., Dineley, K. T., Paessler, S., & Cisneros, I. E. (2024) · Pathogens · doi:10.3390/pathogens13050397 · Cited by 3
Metadata
- Authors
- Lim, C. K., Fernández-Gomez, F. J., Braidy, N., Estrada, C., Costa, C., Costa, S., Bessede, A., Fernandez-Villalba, E., Zinger, A., Herrero, M. T., & Guillemin, G. J.
- Affiliations
- Macquarie University (AU)
- UNSW Sydney (AU)
- Instituto Murciano de Investigación Biosanitaria (ES)
- Universidade Federal da Bahia (BR)
- The University of Sydney (AU)
- St Vincent's Hospital Sydney (AU)
- Corresponding author
- Guillemin, Gilles J.
- Venue
- Progress in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 155
- Pages
- 76-95
- ISSN
- 0301-0082 (ISSN-L)
- OpenAlex
- W2322232345
- Cited by
- 159
- References
- 270
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 19 · 2023: 14 · 2022: 17 · 2021: 22 · 2020: 19 · 2019: 22 · 2018: 6 · 2017: 10
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Spanish Ministry of Science and Innovation (01293)
- European Community’s Seventh Framework Programme (115009)
- Australian Research Council
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Parkinson's disease, kynurenine pathway, tryptophan catabolism, neuroinflammation, microglial activation, kynurenic acid, quinolinic acid, NMDA receptor, excitotoxicity, dopaminergic neuron loss, neuroprotection, NMDA receptor antagonists, biomarkers, therapeutic target
- MeSH terms
- Animals, Humans, Kynurenine, Parkinson Disease
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