ArticlePloS one2012
Sodium phenylbutyrate controls neuroinflammatory and antioxidant activities and protects dopaminergic neurons in mouse models of Parkinson's disease.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Effects of Higher Serum Lipid Levels on the Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis.Frontiers in neurology · 2020Pooled it
- Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.The New England journal of medicine · 2020Trial
- 4-Phenylbutyric acid activates an NF-κB-Egr-1 axis to control myoblast proliferation and ECM gene expression.iScience · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Histone and non-histone (de)acetylation impact on the blood-brain barrier.Fluids and barriers of the CNS · 2026Review
- Beyond Organ Boundaries: Molecular Mechanisms of Hepatic Encephalopathy and Parkinson's Disease from the Perspective of the Gut-Liver-Brain Axis.Research (Washington, D.C.) · 2026Review
- Corrected Version: Neutralization of RANTES and Eotaxin Prevents the Loss of Dopaminergic Neurons in a Mouse Model of Parkinson's Disease.Journal of clinical & experimental immunology · 2026Article
- Short- and Long-Term Effects of Sodium Phenylbutyrate on White Matter and Sensorimotor and Cognitive Behavior in a Mild Murine Model of Encephalopathy of Prematurity.International journal of molecular sciences · 2025Article
- Sodium Phenylbutyrate Ameliorates Ovariectomy-Induced Bone Loss in Rats.Medicina (Kaunas, Lithuania) · 2025Article
- Lipid Metabolism and Statin Therapy in Neurodegenerative Diseases: An Endocrine View.Metabolites · 2025Review
- Drug repurposing in amyotrophic lateral sclerosis (ALS).Expert opinion on drug discovery · 2025Review
- Evaluation of Additive Neuroprotective Effect of Combination Therapy for Parkinson's Disease Using In Vitro Models.Antioxidants (Basel, Switzerland) · 2025Article
- The Therapeutic Potential of Gut-Microbiota-Derived Metabolite 4-Phenylbutyric Acid inInternational journal of molecular sciences · 2025Article
- Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.Nature reviews. Neurology · 2025Review
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- Broad-spectrum therapeutic potential of 4-phenylbutyrate in neurological and systemic diseases of viral and non-viral origin.Frontiers in pharmacology · 2025Review
- Machine learning study on predicting depressive symptoms and genetic correlations in Parkinson's disease.Frontiers in aging neuroscience · 2025Article
- HAT and HDAC: Enzyme with Contradictory Action in Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment.Clinical drug investigation · 2024Review
- Unlocking the epigenetic symphony: histone acetylation's impact on neurobehavioral change in neurodegenerative disorders.Epigenomics · 2024Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that sodium phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI) and farnesyl transferase (FTI) inhibited the activation of NF-κB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21(rac), but not p21(ras), attenuated the production of ROS from activated microglia. Inhibition of both p21(ras) and p21(rac) activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21(ras) and p21(rac)in vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Oral administration of NaPB reduced nigral activation of p21(ras) and p21(rac), protected nigral reduced glutathione, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders.
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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.