ArticleBrain : a journal of neurology2017
Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer's disease mice.
Article in Brain : a journal of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 212 citations in OpenAlex.
- The aging epigenome: integrative analyses reveal intersection with Alzheimer's disease.GeroScience · 2026Pooled it
- Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age.Nature communications · 2019Pooled it
- A biphasic astrocytic PTGDS trajectory marks a metabolic vulnerability stage in prodromal Alzheimer's disease.Research square · 2026Article
- Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026Review
- ZL006 Treatment Reduces Inflammation, Oxidative Stress, and Brain AβInternational journal of molecular sciences · 2026Article
- Mechanistic Insights into Bergapten by Modulation of Filamin A and GSK3β in STZ Induced Alzheimer's Disease: An Integrated In Silico, In Vitro and In Vivo Study.Neurochemical research · 2026Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Region-resolved proteomic map of the human brain: functional interconnections and neurological implications.Signal transduction and targeted therapy · 2026Article
- Hijacking Sodium-Glucose Cotransporters: Fructose Drives Neuronal and Microglial Dysfunction.ASN neuro · 2026Article
- Article
- SFRS8 Regulates Memory by Modulating RNA Splicing of Synaptic Genes.Molecular neurobiology · 2025Article
- Frequency and duration of sensory flicker control transcriptional profiles in 5xFAD mice.APL bioengineering · 2025Article
- Unveiling the role of PSD95 phosphorylation after traumatic brain injury: insights from phosphoproteomic analysis.BMC neurology · 2025Article
- Restoring endogenous Dlg4/PSD95 expression by an artificial transcription factor ameliorates cognitive and motor learning deficits in the R6/2 mouse model of Huntington's disease.Clinical epigenetics · 2025Article
- Target Identification of Ginsenosides Against Cognitive Impairment by Using Mass Spectrometry-Based Cellular Thermal Shift Assay (CETSA).Neurochemical research · 2025Article
- G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.Medicinal research reviews · 2025Review
- Intramuscular delivery of recombinant AAV expressing EpoR76E improves memory and is neuroprotective in 5xFAD transgenics.Research square · 2025Article
- TET1 mitigates prenatal fluoride-induced cognition impairment by modulating Bcl2 DNA hydroxymethylation level.Molecular medicine (Cambridge, Mass.) · 2025Article
- CRISPR-based epigenetic editing of Gad1 improves synaptic inhibition and cognitive behavior in a Tauopathy mouse model.Neurobiology of disease · 2025Article
- Resilience mechanisms underlying Alzheimer's disease.Metabolic brain disease · 2025Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 10 institutions in 3 countries.
Funding
Abstract
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9). These epi-editors altered critical histone marks and subsequently Dlg4/PSD95 expression, which, importantly, impacted several hippocampal neuron plasticity processes. Intriguingly, transduction of the artificial transcription factor PSD95-VP64 rescued memory deficits in aged and Alzheimer's disease mice. Conclusively, this work validates PSD95 as a key player in memory and establishes epigenetic editing as a potential therapy to treat human neurological disorders.
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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.