ArticlePloS one2017
Febuxostat ameliorates secondary progressive experimental autoimmune encephalomyelitis by restoring mitochondrial energy production in a GOT2-dependent manner.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 22 citations in OpenAlex.
- Advances in JNK inhibitor development: therapeutic prospects in neurodegenerative diseases and fibrosis.Archives of pharmacal research · 2025Review
- Gene expression and dispersion profiles associated with water consumption and general activity in grazing beef cattle.Tropical animal health and production · 2025Article
- Extracellular Purine Metabolism-Potential Target in Multiple Sclerosis.Molecular neurobiology · 2024Review
- Blood metabolomic and transcriptomic signatures stratify patient subgroups in multiple sclerosis according to disease severity.iScience · 2024Article
- Investigating the Effect of Cigarette Smoking on Serum Uric Acid Levels in Multiple Sclerosis Patients: A Cross Sectional Study.Brain sciences · 2023Article
- Spotlight on GOT2 in Cancer Metabolism.OncoTargets and therapy · 2023Review
- The complexities of investigating mitochondria dynamics in multiple sclerosis and mouse models of MS.Frontiers in neuroscience · 2023Review
- Regulation of aging by balancing mitochondrial function and antioxidant levels.The journal of physiological sciences : JPS · 2022Article
- Effects of Venlafaxine, Risperidone and Febuxostat on Cuprizone-Induced Demyelination, Behavioral Deficits and Oxidative Stress.International journal of molecular sciences · 2021Article
- New insights in the mechanisms of impaired redox signaling and its interplay with inflammation and immunity in multiple sclerosis.Physiological research · 2020Review
- Febuxostat, a Xanthine Oxidoreductase Inhibitor, Decreases NLRP3-dependent Inflammation in Macrophages by Activating the Purine Salvage Pathway and Restoring Cellular Bioenergetics.Scientific reports · 2019Article
- Computational Drug Repurposing Algorithm Targeting TRPA1 Calcium Channel as a Potential Therapeutic Solution for Multiple Sclerosis.Pharmaceutics · 2019Article
- Shortage of Cellular ATP as a Cause of Diseases and Strategies to Enhance ATP.Frontiers in pharmacology · 2019Article
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Authors and funding
18 authors at 4 institutions in 1 country.
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Abstract
Oxidative stress and mitochondrial dysfunction are important determinants of neurodegeneration in secondary progressive multiple sclerosis (SPMS). We previously showed that febuxostat, a xanthine oxidase inhibitor, ameliorated both relapsing-remitting and secondary progressive experimental autoimmune encephalomyelitis (EAE) by preventing neurodegeneration in mice. In this study, we investigated how febuxostat protects neuron in secondary progressive EAE. A DNA microarray analysis revealed that febuxostat treatment increased the CNS expression of several mitochondria-related genes in EAE mice, most notably including GOT2, which encodes glutamate oxaloacetate transaminase 2 (GOT2). GOT2 is a mitochondrial enzyme that oxidizes glutamate to produce α-ketoglutarate for the Krebs cycle, eventually leading to the production of adenosine triphosphate (ATP). Whereas GOT2 expression was decreased in the spinal cord during the chronic progressive phase of EAE, febuxostat-treated EAE mice showed increased GOT2 expression. Moreover, febuxostat treatment of Neuro2a cells in vitro ameliorated ATP exhaustion induced by rotenone application. The ability of febuxostat to preserve ATP production in the presence of rotenone was significantly reduced by GOT2 siRNA. GOT2-mediated ATP synthesis may be a pivotal mechanism underlying the protective effect of febuxostat against neurodegeneration in EAE. Accordingly, febuxostat may also have clinical utility as a disease-modifying drug in SPMS.
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