ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Epigenetic regulation of motor neuron cell death through DNA methylation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.
What it found
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Who cites it
199 citing papers in PubMed, 360 citations in OpenAlex.
- N 6 -methyladenosine modification regulates cell death in cognitive impairment.Neural regeneration research · 2026Article
- Programmable aging function-related mitochondrial DNA 5-methylcytosine (m5C) modification with a TALE-directed methyltransferase.Cell communication and signaling : CCS · 2026Article
- Longitudinal Analysis of Mitochondrial D-Loop Methylation and Copy Number in Peripheral Blood: Epigenetic Signatures of Alzheimer's Disease Progression and Aging.International journal of molecular sciences · 2026Article
- Dnmt1 Alleviates S1PR1-Mediated Pyroptosis after Spinal Cord Injury through Regulating Pon3 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Resolution of Lipopolysaccharide-Induced Inflammation Followed by DNA Hypomethylation and Increased Tetrahydrobiopterin Biosynthesis in Mouse Hippocampus.Brain sciences · 2025Article
- The role of global DNA methylation in citrinin induced toxicity:Toxicology reports · 2025Article
- Effects of subclinical hypothyroidism during pregnancy on mtDNA methylation in the brain of rat offspring.BMC neuroscience · 2025Article
- Epigenetics Modulators as Therapeutics for Neurological Disorders.Current pharmaceutical design · 2025Review
- Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC.Frontiers in pharmacology · 2025Review
- Mitochondrial epigenetic mechanisms in cancer: an updated overview.Frontiers in cell and developmental biology · 2025Review
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- Mitochondrial epigenetics brings new perspectives on doubly uniparental inheritance in bivalves.Scientific reports · 2024Article
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Exposure to Metals, Pesticides, and Air Pollutants: Focus on Resulting DNA Methylation Changes in Neurodegenerative Diseases.Biomolecules · 2024Review
- Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels.Epigenomes · 2024Article
- Nuclear Localization of Human SOD1 in Motor Neurons in Mouse Model and Patient Amyotrophic Lateral Sclerosis: Possible Links to Cholinergic Phenotype, NADPH Oxidase, Oxidative Stress, and DNA Damage.International journal of molecular sciences · 2024Article
- Article
- Mechanism of motoneuronal and pyramidal cell death in amyotrophic lateral sclerosis and its potential therapeutic modulation.Cell death discovery · 2024Review
- Mitochondrial One-Carbon Metabolism and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Review
139 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
DNA methylation is an epigenetic mechanism for gene silencing engaged by DNA methyltransferase (Dnmt)-catalyzed methyl group transfer to cytosine residues in gene-regulatory regions. It is unknown whether aberrant DNA methylation can cause neurodegeneration. We tested the hypothesis that Dnmts can mediate neuronal cell death. Enforced expression of Dnmt3a induced degeneration of cultured NSC34 cells. During apoptosis of NSC34 cells induced by camptothecin, levels of Dnmt1 and Dnmt3a increased fivefold and twofold, respectively, and 5-methylcytosine accumulated in nuclei. Truncation mutation of the Dnmt3a catalytic domain and Dnmt3a RNAi blocked apoptosis of cultured neurons. Inhibition of Dnmt catalytic activity with RG108 and procainamide protected cultured neurons from excessive DNA methylation and apoptosis. In vivo, Dnmt1 and Dnmt3a are expressed differentially during mouse brain and spinal cord maturation and in adulthood when Dnmt3a is abundant in synapses and mitochondria. Dnmt1 and Dnmt3a are expressed in motor neurons of adult mouse spinal cord, and, during their apoptosis induced by sciatic nerve avulsion, nuclear and cytoplasmic 5-methylcytosine immunoreactivity, Dnmt3a protein levels and Dnmt enzyme activity increased preapoptotically. Inhibition of Dnmts with RG108 blocked completely the increase in 5-methycytosine and the apoptosis of motor neurons in mice. In human amyotrophic lateral sclerosis (ALS), motor neurons showed changes in Dnmt1, Dnmt3a, and 5-methylcytosine similar to experimental models. Thus, motor neurons can engage epigenetic mechanisms to drive apoptosis, involving Dnmt upregulation and increased DNA methylation. These cellular mechanisms could be relevant to human ALS pathobiology and disease treatment.
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Registered trials
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