ArticleExperimental neurology2015
Bromodomain inhibitors regulate the C9ORF72 locus in ALS.
Article in Experimental neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- IGF2BPs directly regulate the noncanonical translation of toxic proteins from mutant FMR1 mRNA containing expanded CGG repeats.Nature communications · 2025Article
- High-throughput screen of 100 000 small molecules in C9ORF72 ALS neurons identifies spliceosome modulators that mobilize G4C2 repeat RNA into nuclear export and repeat associated non-canonical translation.Nucleic acids research · 2025Article
- Epigenetics in Neurodegenerative Diseases.Sub-cellular biochemistry · 2025Review
- Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- Bromodomain and Extra-Terminal Proteins in Brain Physiology and Pathology: BET-ing on Epigenetic Regulation.Biomedicines · 2023Review
- Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration.Cell & bioscience · 2023Review
- CRISPR/Cas9-mediated excision of ALS/FTD-causing hexanucleotide repeat expansion in C9ORF72 rescues major disease mechanisms in vivo and in vitro.Nature communications · 2022Article
- Epigenetic Changes and Chromatin Reorganization in Brain Function: Lessons from Fear Memory Ensemble and Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Epigenetic Small Molecules Rescue Nucleocytoplasmic Transport and DNA Damage Phenotypes in C9ORF72 ALS/FTD.Brain sciences · 2021Article
- Correction of Heritable Epigenetic Defects Using Editing Tools.International journal of molecular sciences · 2021Review
- BET bromodomain inhibitors PFI-1 and JQ1 are identified in an epigenetic compound screen to enhance C9ORF72 gene expression and shown to ameliorate C9ORF72-associated pathological and behavioral abnormalities in a C9ALS/FTD model.Clinical epigenetics · 2021Article
- Dual Screen for Efficacy and Toxicity Identifies HDAC Inhibitor with Distinctive Activity Spectrum for BAP1-Mutant Uveal Melanoma.Molecular cancer research : MCR · 2021Article
- BET bromodomains as novel epigenetic targets for brain health and disease.Neuropharmacology · 2020Review
- Dipeptide repeat proteins inhibit homology-directed DNA double strand break repair in C9ORF72 ALS/FTD.Molecular neurodegeneration · 2020Article
- Enhancement of BDNF Expression and Memory by HDAC Inhibition Requires BET Bromodomain Reader Proteins.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Molecular Mechanisms of Neurodegeneration Related toBehavioural neurology · 2019Review
- C9orf72-mediated ALS and FTD: multiple pathways to disease.Nature reviews. Neurology · 2018Review
- Development of Therapeutics for C9ORF72 ALS/FTD-Related Disorders.Molecular neurobiology · 2017Review
- A C9ORF72 BAC mouse model recapitulates key epigenetic perturbations of ALS/FTD.Molecular neurodegeneration · 2017Article
- Emerging Epigenetic Therapies in Neuroscience: Focus on Bromodomain-Containing Drug Targets.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
A hexanucleotide repeat expansion residing within the C9ORF72 gene represents the most common known cause of amyotrophic lateral sclerosis (ALS) and places the disease among a growing family of repeat expansion disorders. The presence of RNA foci, repeat-associated translation products, and sequestration of RNA binding proteins suggests that toxic RNA gain-of-function contributes to pathology while C9ORF72 haploinsufficiency may be an additional pathological factor. One viable therapeutic strategy for treating expansion diseases is the use of small molecule inhibitors of epigenetic modifier proteins to reactivate expanded genetic loci. Indeed, previous studies have established proof of this principle by increasing the drug-induced expression of expanded (and abnormally heterochromatinized) FMR1, FXN and C9ORF72 genes in respective patient cells. While epigenetic modifier proteins are increasingly recognized as druggable targets, there have been few screening strategies to address this avenue of drug discovery in the context of expansion diseases. Here we utilize a semi-high-throughput gene expression based screen to identify siRNAs and small molecule inhibitors of epigenetic modifier proteins that regulate C9ORF72 RNA in patient fibroblasts, lymphocytes and reprogrammed motor neurons. We found that several bromodomain small molecule inhibitors increase the expression of C9ORF72 mRNA and pre-mRNA without affecting repressive epigenetic signatures of expanded C9ORF72 alleles. These data suggest that bromodomain inhibition increases the expression of unexpanded C9ORF72 alleles and may therefore compensate for haploinsufficiency without increasing the production of toxic RNA and protein products, thereby conferring therapeutic value.
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