ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
Targeting the HDAC2/HNF-4A/miR-101b/AMPK Pathway Rescues Tauopathy and Dendritic Abnormalities in Alzheimer's Disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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71 citing papers in PubMed, 122 citations in OpenAlex.
- Gut microbiota as a modulator of HDAC: insights into Alzheimer's disease treatment.Pharmacological reports : PR · 2026Review
- The NLRP3 inflammasome: pathophysiology and therapeutic implications for schizophrenia and neuropsychiatric disorders.Molecular psychiatry · 2026Review
- Targeting Histone Deacetylase 2 in Alzheimer's Disease: From Molecular Insights to Epigenetic Therapeutic Opportunities.Molecular neurobiology · 2026Review
- MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.Neural regeneration research · 2026Article
- A computational framework for epigenetic plasticity in memory.Brain : a journal of neurology · 2026Review
- Aerobic exercise facilitates p300 nuclear translocation via ADRB2-AMPKα signaling, leading to enhanced histone acetylation and mitigation of cognitive decline in APP/PS1 mice.Alzheimer's research & therapy · 2026Article
- Ferroptosis-associated transcriptional factors in neurological diseases: molecular mechanisms and therapeutic prospects.Experimental & molecular medicine · 2025Review
- Histone Deacetylase 2 in Alzheimer's Disease: A Comprehensive Molecular Blueprint for Therapeutic Targeting.Molecular neurobiology · 2025Review
- Multiple Mechanisms and Therapeutic Strategies for the Involvement of AMPK in the Development of Alzheimer's Disease.Molecular neurobiology · 2025Review
- Targeting the miR-96-5p/Cathepsin B Pathway to Alleviate Neuron-Derived Neuroinflammation in Alzheimer's Disease.MedComm · 2025Article
- Review
- CoREST3 exhibits isoform specific expression in Alzheimer's disease and regulation of HDAC2.BMC biology · 2025Article
- Total Flavones ofCurrent issues in molecular biology · 2025Article
- Rhynchophylline alleviates cognitive deficits in multiple transgenic mouse models of Alzheimer's disease via modulating neuropathology and gut microbiota.Acta pharmacologica Sinica · 2025Article
- Histone Deacetylation in Alzheimer's Diseases (AD); Hope or Hype.Cell biochemistry and biophysics · 2025Review
- TRAPT: a multi-stage fused deep learning framework for predicting transcriptional regulators based on large-scale epigenomic data.Nature communications · 2025Article
- Tau Pathology Drives Disease-Associated Astrocyte Reactivity in Salt-Induced Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A review on gut microbiota and miRNA crosstalk: implications for Alzheimer's disease.GeroScience · 2025Review
- Periodontal Tissue Homoeostasis, Immunity, the Red Complex Pathogens, and Dysbiosis: Unraveling the microRNA Effect.MicroRNA (Shariqah, United Arab Emirates) · 2025Review
- Histone Deacetylase Inhibition in Alzheimer's Disease: Molecular Mechanisms, Therapeutic Potential, and Future Perspectives.Current topics in medicinal chemistry · 2025Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase 2 (HDAC2) plays a major role in the epigenetic regulation of gene expression. Previous studies have shown that HDAC2 expression is strongly increased in Alzheimer's disease (AD), a major neurodegenerative disorder and the most common form of dementia. Moreover, previous studies have linked HDAC2 to Aβ overproduction in AD; however, its involvement in tau pathology and other memory-related functions remains unclear. Here, we show that increased HDAC2 levels strongly correlate with phosphorylated tau in a mouse model of AD. HDAC2 overexpression induced AD-like tau hyperphosphorylation and aggregation, which were accompanied by a loss of dendritic complexity and spine density. The ectopic expression of HDAC2 resulted in the deacetylation of the hepatocyte nuclear factor 4α (HNF-4A) transcription factor, which disrupted its binding to the miR-101b promoter. The suppression of miR-101b caused an upregulation of its target, AMP-activated protein kinase (AMPK). The introduction of miR-101b mimics or small interfering RNAs (siRNAs) against AMPK blocked HDAC2-induced tauopathy and dendritic impairments in vitro. Correspondingly, miR-101b mimics or AMPK siRNAs rescued tau pathology, dendritic abnormalities, and memory deficits in AD mice. Taken together, the current findings implicate the HDAC2/miR-101/AMPK pathway as a critical mediator of AD pathogenesis. These studies also highlight the importance of epigenetics in AD and provide novel therapeutic targets.
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