ArticleJournal of neurochemistry2010
Dysfunctional kynurenine pathway metabolism in the R6/2 mouse model of Huntington's disease.
Article in Journal of neurochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 66 citations in OpenAlex.
- Significance of NAD anabolism profiles in neurological diseases.Metabolic brain disease · 2026Review
- Cell Signaling by Tryptophan Catabolism.Biochemistry · 2026Review
- Role of Kynurenine and Its Derivatives in Liver Diseases: Recent Advances and Future Clinical Perspectives.International journal of molecular sciences · 2025Review
- Kynurenine monooxygenaseFrontiers in microbiology · 2025Article
- Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.Pharmacological reviews · 2024Review
- The Complex World of Kynurenic Acid: Reflections on Biological Issues and Therapeutic Strategy.International journal of molecular sciences · 2024Review
- Role of Kynurenine and Its Derivatives in the Neuroimmune System.International journal of molecular sciences · 2024Review
- Kynurenine 3-Monooxygenase Interacts with Huntingtin at the Outer Mitochondrial Membrane.Biomedicines · 2022Article
- Cellular Localization of Kynurenine 3-Monooxygenase in the Brain: Challenging the Dogma.Antioxidants (Basel, Switzerland) · 2022Article
- Kynurenic acid in neurodegenerative disorders-unique neuroprotection or double-edged sword?CNS neuroscience & therapeutics · 2022Review
- Converging evidence in support of omega-3 polyunsaturated fatty acids as a potential therapy for Huntington's disease symptoms.Reviews in the neurosciences · 2021Review
- Kynurenine pathway metabolites in cerebrospinal fluid and blood as potential biomarkers in Huntington's disease.Journal of neurochemistry · 2021Article
- Review
- Ablation of kynurenine 3-monooxygenase rescues plasma inflammatory cytokine levels in the R6/2 mouse model of Huntington's disease.Scientific reports · 2021Article
- Neuroimmune crosstalk and evolving pharmacotherapies in neurodegenerative diseases.Immunology · 2021Review
- Advantages of brain penetrating inhibitors of kynurenine-3-monooxygenase for treatment of neurodegenerative diseases.Archives of biochemistry and biophysics · 2021Review
- Potential Mechanism of Cellular Uptake of the Excitotoxin Quinolinic Acid in Primary Human Neurons.Molecular neurobiology · 2021Article
- Kynurenine-3-monooxygenase: A new direction for the treatment in different diseases.Food science & nutrition · 2020Review
- IDO and Kynurenine Metabolites in Peripheral and CNS Disorders.Frontiers in immunology · 2020Review
- Therapeutic approaches to Huntington disease: from the bench to the clinic.Nature reviews. Drug discovery · 2018Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Elevated concentrations of neurotoxic metabolites of the kynurenine pathway (KP) of tryptophan degradation may play a causative role in Huntington's disease (HD). The brain levels of one of these compounds, 3-hydroxykynurenine (3-HK), are increased in both HD and several mouse models of the disease. In the present study, we examined this impairment in greater detail using the R6/2 mouse, a well-established animal model of HD. Initially, mutant and age-matched wild-type mice received an intrastriatal injection of (3)H-tryptophan to assess the acute, local de novo production of kynurenine, the immediate bioprecursor of 3-HK, in vivo. No effect of genotype was observed between 4 and 12 weeks of age. In contrast, intrastriatally applied (3)H-kynurenine resulted in significantly increased neosynthesis of (3)H-3-HK, but not other tritiated KP metabolites, in the R6/2 striatum. Subsequent ex vivo studies in striatal, cortical and cerebellar tissue revealed substantial increases in the activity of the biosynthetic enzyme of 3-HK, kynurenine 3-monooxygenase and significant reductions in the activity of its degradative enzyme, kynureninase, in HD mice starting at 4 weeks of age. Decreased kynureninase activity was most evident in the cortex and preceded the increase in kynurenine 3-monooxygenase activity. The activity of other KP enzymes showed no consistent brain abnormalities in the mutant mice. These findings suggest that impairments in its immediate metabolic enzymes jointly account for the abnormally high brain levels of 3-HK in the R6/2 model of HD.
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Registered trials
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