ArticleScientific reports2016
Inhibition of DNA Methyltransferases Blocks Mutant Huntingtin-Induced Neurotoxicity.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers, 1 of them a synthesis that pooled it.
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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- The role of AI-assisted drug repurposing in neurological disorders: a systematic review of validation strategies, challenges and opportunities.Journal of nanobiotechnology · 2026Pooled it
- Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.Molecular neurodegeneration · 2026Article
- Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Article
- Sustained Epigenetic Reactivation in Fragile X Neurons with an RNA-Binding Small Molecule.Genes · 2025Article
- Epigenetics Modulators as Therapeutics for Neurological Disorders.Current pharmaceutical design · 2025Review
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- Review
- Neuroinflammation and the role of epigenetic-based therapies for Huntington's disease management: the new paradigm.Inflammopharmacology · 2024Review
- Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease.Frontiers in cellular neuroscience · 2024Review
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- Review
- The DNA Methylation in Neurological Diseases.Cells · 2022Review
- DNA Methylation: A Promising Approach in Management of Alzheimer's Disease and Other Neurodegenerative Disorders.Biology · 2022Review
- Role of DNMTs in the Brain.Advances in experimental medicine and biology · 2022Review
- DNA Methylation in Huntington's Disease.International journal of molecular sciences · 2021Review
- Epigenetic regulation in Huntington's disease.Neurochemistry international · 2021Review
- Chromatin Alterations in Neurological Disorders and Strategies of (Epi)Genome Rescue.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Epigenomic Remodeling in Huntington's Disease-Master or Servant?Epigenomes · 2020Review
- DNA Methyltransferase 1 (DNMT1) Acts on Neurodegeneration by Modulating Proteostasis-Relevant Intracellular Processes.International journal of molecular sciences · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Although epigenetic abnormalities have been described in Huntington's disease (HD), the causal epigenetic mechanisms driving neurodegeneration in HD cortex and striatum remain undefined. Using an epigenetic pathway-targeted drug screen, we report that inhibitors of DNA methyltransferases (DNMTs), decitabine and FdCyd, block mutant huntingtin (Htt)-induced toxicity in primary cortical and striatal neurons. In addition, knockdown of DNMT3A or DNMT1 protected neurons against mutant Htt-induced toxicity, together demonstrating a requirement for DNMTs in mutant Htt-triggered neuronal death and suggesting a neurodegenerative mechanism based on DNA methylation-mediated transcriptional repression. Inhibition of DNMTs in HD model primary cortical or striatal neurons restored the expression of several key genes, including Bdnf, an important neurotrophic factor implicated in HD. Accordingly, the Bdnf promoter exhibited aberrant cytosine methylation in mutant Htt-expressing cortical neurons. In vivo, pharmacological inhibition of DNMTs in HD mouse brains restored the mRNA levels of key striatal genes known to be downregulated in HD. Thus, disturbances in DNA methylation play a critical role in mutant Htt-induced neuronal dysfunction and death, raising the possibility that epigenetic strategies targeting abnormal DNA methylation may have therapeutic utility in HD.
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What OpenQuestion holds
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.