ArticleNature communications2023
Inhibition of histone methyltransferase Smyd3 rescues NMDAR and cognitive deficits in a tauopathy mouse model.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- DNA Methylation and Proteomic Profiling of Postmortem Brain Tissue Reveals Epigenetic Dysregulation and Neuroinflammatory in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).bioRxiv : the preprint server for biology · 2026Article
- Targeted neuronal reprogramming rescues memory and neural synchrony in Alzheimer's disease.Molecular biomedicine · 2026Article
- Histone modification dynamics in brain aging: unlocking therapeutic potential.Cell death & disease · 2026Review
- Diminished activity-dependent neuroprotective protein (ADNP) contributes to complement gene elevation in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Epigenomic aberrations of histone methylation in prefrontal cortex of humans with mild cognitive impairment and Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Histone demethylase PHF2 regulates inflammatory genes in Alzheimer's disease.Molecular psychiatry · 2026Article
- From correlation to causation: cell-type-specific gene regulatory networks in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Research advancements regarding the relationship between FBXO2 and malignant tumors (Review).Molecular medicine reports · 2025Review
- From Correlation to Causation: Cell-Type-Specific Gene Regulatory Networks in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2025Article
- SMYD3 Promotes Immune Evasion in Clear Cell Renal Cell Carcinoma via SREBP1-Mediated Transactivation of CD47.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Identification of Transdiagnostic Childhood Externalizing Pathology Within an Electronic Medical Records Database and Application to the Analysis of Rare Copy Number Variation.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2025Article
- CRISPR-based epigenetic editing of Gad1 improves synaptic inhibition and cognitive behavior in a Tauopathy mouse model.Neurobiology of disease · 2025Article
- FBXO2 as a switch guides a special fate of tumor clones evolving into a highly malignant transcriptional subtype in oral squamous cell carcinoma.Apoptosis : an international journal on programmed cell death · 2025Article
- FBXO2 promotes hepatocellular carcinoma progression and sorafenib resistance by targeting USP49 for proteasomal degradation.Frontiers in immunology · 2025Article
- Genome-wide association neural networks identify genes linked to family history of Alzheimer's disease.Briefings in bioinformatics · 2024Article
- Histone Methylation, Energy Metabolism, and Alzheimer's Disease.Aging and disease · 2024Review
- Endoplasmic reticulum stress-induced senescence in human lung fibroblasts.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- An Overview of the Epigenetic Modifications in the Brain under Normal and Pathological Conditions.International journal of molecular sciences · 2024Review
- Distinct and Convergent Alterations of Entorhinal Cortical Circuits in Two Mouse Models for Alzheimer's Disease and Related Disorders.Journal of Alzheimer's disease : JAD · 2024Article
- Hippocampal hyperphosphorylated tau-induced deficiency is rescued by L-type calcium channel blockade.Brain communications · 2024Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Pleiotropic mechanisms have been implicated in Alzheimer's disease (AD), including transcriptional dysregulation, protein misprocessing and synaptic dysfunction, but how they are mechanistically linked to induce cognitive deficits in AD is unclear. Here we find that the histone methyltransferase Smyd3, which catalyzes histone H3 lysine 4 trimethylation (H3K4me3) to activate gene transcription, is significantly elevated in prefrontal cortex (PFC) of AD patients and P301S Tau mice, a model of tauopathies. A short treatment with the Smyd3 inhibitor, BCI-121, rescues cognitive behavioral deficits, and restores synaptic NMDAR function and expression in PFC pyramidal neurons of P301S Tau mice. Fbxo2, which encodes an E3 ubiquitin ligase controlling the degradation of NMDAR subunits, is identified as a downstream target of Smyd3. Smyd3-induced upregulation of Fbxo2 in P301S Tau mice is linked to the increased NR1 ubiquitination. Fbxo2 knockdown in PFC leads to the recovery of NMDAR function and cognitive behaviors in P301S Tau mice. These data suggest an integrated mechanism and potential therapeutic strategy for AD.
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