ArticleEpigenetics2020
Betaine restores epigenetic control and supports neuronal mitochondria in the cuprizone mouse model of multiple sclerosis.
Article in Epigenetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Betaine-driven Keap1 methylation promotes p62-mediated autophagy and Nrf2 stabilization to alleviate glutathione-dependent redox dyshomeostasis in liver injury.Molecular biomedicine · 2026Article
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.Molecular and cellular biochemistry · 2026Review
- Sulfur-Containing Amino Acid Homeostasis in the Central Nervous System: From Physiology Regulation to Metal-Induced Neurotoxicity.Metabolites · 2026Review
- Betaine: A Promising Natural Product for Neurological and Psychiatric Diseases.Current neuropharmacology · 2026Review
- Betaine as a regulator of metabolism, epigenetics, and cellular osmoprotection: therapeutic implications in cardiometabolic and renal diseases.Frontiers in pharmacology · 2026Review
- Serum Metabolomics Reveals Potential Differences in Gut Microbiota-Associated Metabolites in Twins Discordant for Type 1 Diabetes.Diabetes · 2025Article
- Epigenetic and Mitochondrial Metabolic Dysfunction in Multiple Sclerosis: A Review of Herbal Drug Approaches and Current Clinical Trials.Molecular neurobiology · 2025Review
- Network pharmacology and metabolomics analysis of Tinospora cordifolia reveals BACE1 and MAOB as potential therapeutic targets for neuroprotection in Alzheimer's disease.Scientific reports · 2025Article
- Role of Vanin-1 Gene Methylation in Fat Synthesis in Goose Liver: Effects of Betaine and 5-Azacytidine Treatments.Animals : an open access journal from MDPI · 2025Article
- Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis.Frontiers in immunology · 2025Article
- Effect of betaine on growth performance, methionine metabolism, and methyl transfer in broilers aged 1 to 21 days and fed a low-methionine diet.The journal of poultry science · 2025Article
- Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase (G6PD) by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis.Science China. Life sciences · 2024Article
- Association of homocysteine with white matter dysconnectivity in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
- Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an mRedox biology · 2024Article
- Histone methylation in Epstein-Barr virus-associated diseases.Epigenomics · 2024Review
- FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment.Cell death & disease · 2023Article
- Molecular Mechanisms Provide a Landscape for Biomarker Selection for Schizophrenia and Schizoaffective Psychosis.International journal of molecular sciences · 2023Review
- Mitochondrial dysfunction in neurodegenerative disorders: Potential therapeutic application of mitochondrial transfer to central nervous system-residing cells.Journal of translational medicine · 2023Review
- Betaine as a Functional Ingredient: Metabolism, Health-Promoting Attributes, Food Sources, Applications and Analysis Methods.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methionine metabolism is dysregulated in multiple sclerosis (MS). The methyl donor betaine is depleted in the MS brain where it is linked to changes in levels of histone H3 trimethylated on lysine 4 (H3K4me3) and mitochondrial impairment. We investigated the effects of replacing this depleted betaine in the cuprizone mouse model of MS. Supplementation with betaine restored epigenetic control and alleviated neurological disability in cuprizone mice. Betaine increased the methylation potential (SAM/SAH ratio), levels of H3K4me3, enhanced neuronal respiration, and prevented axonal damage. We show that the methyl donor betaine and the betaine homocysteine methyltransferase (BHMT) enzyme can act in the nucleus to repair epigenetic control and activate neuroprotective transcriptional programmes. ChIP-seq data suggest that BHMT acts on chromatin to increase the SAM/SAH ratio and histone methyltransferase activity locally to increase H3K4me3 and activate gene expression that supports neuronal energetics. These data suggest that the methyl donor betaine may provide neuroprotection in MS where mitochondrial impairment damages axons and causes disability.
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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.