ArticleMolecular psychiatry2022
Targeting histone demethylase LSD1 for treatment of deficits in autism mouse models.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Efficacy of pharmacological and microbiota-based therapies in preclinical models of autism spectrum disorder: a systematic review.Molecular psychiatry · 2026Pooled it
- Unraveling the Role of Wnt Signaling Pathway in the Pathogenesis of Autism Spectrum Disorder (ASD): A Systematic Review.Molecular neurobiology · 2025Pooled it
- Epigenetic treatment of synaptic and behavioral deficits in Dyrk1a-mutant mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Autism-like phenotypes and increased NMDAR2D expression in mice with KDM5B histone lysine demethylase deficiency.Science advances · 2026Article
- JUND-driven stress-responsive astrocytes promote neuronal apoptosis via enhanced gap junction signaling in autism spectrum disorder.Molecular autism · 2026Article
- Epigenetic and Transcriptomic Pathways Underlying Animal Models of Cognitive and Psychiatric Disorders: A Scoping Review.Current issues in molecular biology · 2026Review
- ORY1001 enhances anti-tumor immunity via CXCL10-mediated macrophage modulation in EBV-positive DLBCL.Cell communication and signaling : CCS · 2026Article
- Modifications on histone tails in psychiatric disorders.EC psychology and psychiatry · 2026Article
- Inhalation exposure to tire rubber particle-sourced pollutant 6PPD-quinone involving basolateral amygdala impairment in male ICR mice.Journal of advanced research · 2026Article
- Inhibition of histone lysine demethylase restores learning and memory in aged mice.bioRxiv : the preprint server for biology · 2025Article
- Chromatin remodeling factor BAF155 coordinates oligodendroglial-neuronal communications linked to regional myelination and autism-like behavioral deficits in mice.Nature communications · 2025Article
- Targeting Histone H3K9 Methyltransferase G9a as a Potential Therapeutic Strategy for Neuropsychiatric Disorders.Medicinal research reviews · 2025Review
- Recapitulation and reversal of neuropsychiatric phenotypes in a mouse model of human endogenous retrovirus type W expression.Molecular psychiatry · 2025Article
- Synaptic Deficits in Adnp-Mutant Mice Are Ameliorated by Histone Demethylase LSD1 Inhibition.Autism research : official journal of the International Society for Autism Research · 2025Article
- Emerging Epigenetic Therapeutics and Diagnostics for Autism Spectrum Disorder.Current issues in molecular biology · 2025Review
- The multifaceted role of post-translational modifications of LSD1 in cellular processes and disease pathogenesis.Genes & diseases · 2025Review
- Vafidemstat: a lysine-specific demethylase 1A inhibitor that shows promise for treating neuropsychiatric disorders.Epigenetics reports · 2025Article
- Phenotype and psychometric characterization of Phelan-McDermid syndrome patients: pioneering towards personalized medicine.Frontiers in psychiatry · 2025Article
- The Use of Nutraceutical and Pharmacological Strategies in Murine Models of Autism Spectrum Disorder.Cells · 2024Review
- Targeting epigenetic enzymes for autism treatment.Trends in pharmacological sciences · 2024Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Large-scale genetic studies have revealed that the most prominent genes disrupted in autism are chromatin regulators mediating histone methylation/demethylation, suggesting the central role of epigenetic dysfunction in this disorder. Here, we show that histone lysine 4 dimethylation (H3K4me2), a histone mark linked to gene activation, is significantly decreased in the prefrontal cortex (PFC) of autistic human patients and mutant mice with the deficiency of top-ranking autism risk factor Shank3 or Cul3. A brief treatment of the autism models with highly potent and selective inhibitors of the H3K4me2 demethylase LSD1 (KDM1A) leads to the robust rescue of core symptoms of autism, including social deficits and repetitive behaviors. Concomitantly, LSD1 inhibition restores NMDA receptor function in PFC and AMPA receptor-mediated currents in striatum of Shank3-deficient mice. Genome-wide RNAseq and ChIPseq reveal that treatment of Shank3-deficient mice with the LSD1 inhibitor restores the expression and H3K4me2 occupancy of downregulated genes enriched in synaptic signaling and developmental processes. The immediate early gene tightly linked to neuronal plasticity, Egr1, is on the top list of rescued genes. The diminished transcription of Egr1 is recapitulated in PFC of autistic human patients. Overexpression of Egr1 in PFC of Shank3-deficient mice ameliorates social preference deficits. These results have for the first time revealed an important role of H3K4me2 abnormality in ASD pathophysiology, and the therapeutic potential of targeting H3K4me2 demethylase LSD1 or the downstream molecule Egr1 for ASD.
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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.