ArticleJournal of Alzheimer's disease : JAD2012
Metabolism and neurotoxicity of homocysteine thiolactone in mice: evidence for a protective role of paraoxonase 1.
Article in Journal of Alzheimer's disease : JAD, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 69 citations in OpenAlex.
- Urinary excretion of homocysteine thiolactone and the risk of acute myocardial infarction in coronary artery disease patients: the WENBIT trial.Journal of internal medicine · 2019Trial
- Homocysteine Metabolites, Endothelial Dysfunction, and Cardiovascular Disease.International journal of molecular sciences · 2025Review
- Human Paraoxonase 1: From Bloodstream Enzyme to Disease Fighter & Therapeutic Intervention.Current protein & peptide science · 2025Review
- The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1.Antioxidants (Basel, Switzerland) · 2024Review
- Discovery of a novel homocysteine thiolactone hydrolase and the catalytic activity of its natural variants.Protein science : a publication of the Protein Society · 2024Article
- Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Appraising the Role of Astrocytes as Suppliers of Neuronal Glutathione Precursors.International journal of molecular sciences · 2023Review
- Proteomic Exploration of Paraoxonase 1 Function in Health and Disease.International journal of molecular sciences · 2023Review
- Article
- Modulatory Effect of Lifestyle-Related, Environmental and Genetic Factors on Paraoxonase-1 Activity: A Review.International journal of environmental research and public health · 2023Review
- Homocysteine, Vitamins B6 and Folic Acid in Experimental Models of Myocardial Infarction and Heart Failure-How Strong Is That Link?Biomolecules · 2022Review
- Reduced paraoxonase 1 activities may explain the comorbidities between temporal lobe epilepsy and depression, anxiety and psychosis.World journal of psychiatry · 2022Article
- Genetic Attenuation of Paraoxonase 1 Activity Induces Proatherogenic Changes in Plasma Proteomes of Mice and Humans.Antioxidants (Basel, Switzerland) · 2020Article
- Pomegranate Seed Oil and Bitter Melon Extract Affect Fatty Acids Composition and Metabolism in Hepatic Tissue in Rats.Molecules (Basel, Switzerland) · 2020Article
- Paraoxonase 1 Phenotype and Protein N-Homocysteinylation in Patients with Rheumatoid Arthritis: Implications for Cardiovascular Disease.Antioxidants (Basel, Switzerland) · 2020Article
- Inhibiting MARSs reduces hyperhomocysteinemia-associated neural tube and congenital heart defects.EMBO molecular medicine · 2020Article
- Paraoxonases Activities and Polymorphisms in Elderly and Old-Age Diseases: An Overview.Antioxidants (Basel, Switzerland) · 2019Review
- Daily supplementation with fresh pomegranate juice increases paraoxonase 1 expression and activity in mice fed a high-fat diet.European journal of nutrition · 2018Article
- Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance.Frontiers in neuroscience · 2016Review
- Mechanisms involved in the ischemic tolerance in brain: effect of the homocysteine.Cellular and molecular neurobiology · 2015Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Homocysteine (Hcy)-thiolactone is toxic, induces epileptic seizures in rodents, and has been implicated in Alzheimer's disease. Paraoxonase 1 (Pon1), a component of high-density lipoprotein, hydrolyzes Hcy-thiolactone in vitro. Whether this reflects a physiological function and whether Pon1 can protect against Hcy-thiolactone toxicity was unknown. Here we show that Hcy-thiolactone was elevated in brains of Pon1-/- mice (1.5-fold, p = 0.047) and that Pon1-/- mice excrete more Hcy-thiolactone than wild type animals (2.4-fold, p = 0.047). The frequency of seizures induced by intraperitoneal injections of L-Hcy-thiolactone was significantly higher in Pon1-/- mice compared with wild type animals (52.8% versus 29.5%, p = 0.042); the latency of seizures was lower in Pon1-/- mice than in wild type animals (31.8 min versus 41.2 min, p = 0.019). Using the Pon1 null mice, we provide the first direct evidence that a specific Hcy metabolite, Hcy-thiolactone, rather than Hcy itself is neurotoxic in vivo. Our findings indicate that Pon1 protects mice against Hcy-thiolactone neurotoxicity by hydrolyzing it in the brain, and suggest a mechanism by which Pon1 can protect against neurodegeneration associated with hyperhomocysteinemia and Alzheimer's disease.
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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.