ArticleNeurobiology of disease2015
Neuroprotective effects of urate are mediated by augmenting astrocytic glutathione synthesis and release.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- Dissociation between urate and blood pressure in mice and in people with early Parkinson's disease.EBioMedicine · 2018Trial
- A review of the evidence for a protective role of uric acid in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Uric Acid, the End-Product of Purine Metabolism, Mitigates Tau-Related Abnormalities: Comparison with DOT, a Non-Antibiotic Oxytetracycline Derivative.Biomolecules · 2025Article
- White matter integrity mediated the effect of plasma uric acid levels on cognitive function in ALS patients.Brain imaging and behavior · 2025Article
- Targeting uric acid: a promising intervention against oxidative stress and neuroinflammation in neurodegenerative diseases.Cell communication and signaling : CCS · 2025Review
- Association between gout, hyperuricaemia and Parkinson's disease risk: a cohort study in western Sweden (2001-2017).Rheumatology advances in practice · 2025Article
- Biological sex impacts oxidative stress in skeletal muscle in a porcine heat stress model.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- Neuroprotective Strategies and Cell-Based Biomarkers for Manganese-Induced Toxicity in Human Neuroblastoma (SH-SY5Y) Cells.Biomolecules · 2024Article
- Comprehensive blood metabolomics profiling of Parkinson's disease reveals coordinated alterations in xanthine metabolism.NPJ Parkinson's disease · 2024Article
- Role of Astrogliosis in the Pathogenesis of Parkinson's Disease: Insights into Astrocytic Nrf2 Pathway as a Potential Therapeutic Target.CNS & neurological disorders drug targets · 2024Review
- Disorders of Endogenous and Exogenous Antioxidants in Neurological Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson's disease.Scientific reports · 2023Article
- Glutathione-Mediated Neuroprotective Effect of Purine Derivatives.International journal of molecular sciences · 2023Review
- Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?International journal of molecular sciences · 2022Review
- Melanocortin 1 receptor activation protects against alpha-synuclein pathologies in models of Parkinson's disease.Molecular neurodegeneration · 2022Article
- Plasma Uric Acid Helps Predict Cognitive Impairment in Patients With Amyotrophic Lateral Sclerosis.Frontiers in neurology · 2021Article
- Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway.Journal of immunology research · 2021Article
- Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration.International journal of molecular sciences · 2020Review
- Nonsteroidal Anti-inflammatory Use and LRRK2 Parkinson's Disease Penetrance.Movement disorders : official journal of the Movement Disorder Society · 2020Article
- Genetically Determined Uric Acid and the Risk of Cardiovascular and Neurovascular Diseases: A Mendelian Randomization Study of Outcomes Investigated in Randomized Trials.Journal of the American Heart Association · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Urate has emerged as a promising target for neuroprotection based on epidemiological observations, preclinical models, and early clinical trial results in multiple neurologic diseases, including Parkinson's disease (PD). This study investigates the astrocytic mechanism of urate's neuroprotective effect. Targeted biochemical screens of conditioned medium from urate- versus vehicle-treated astrocytes identified markedly elevated glutathione (GSH) concentrations as a candidate mediator of urate's astrocyte-dependent neuroprotective effects. Urate treatment also induced the nuclear translocation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein and transcriptional activation of its key target genes in primary astrocytic cultures. Urate's neuroprotective effect was attenuated when GSH was depleted in the conditioned media either by targeting its synthesis or release by astrocytes. Overall, these results implicate GSH as the extracellular astrocytic factor mediating the protective effect of urate in a cellular model of PD. These results also show that urate can employ a novel indirect neuroprotective mechanism via induction of the Nrf2 signaling pathway, a master regulator of the response to oxidative stress, in astrocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.