ArticleNature genetics2018
CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.
Article in Nature genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 2 of them syntheses that pooled it.
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Who cites it
141 citing papers in PubMed, 2 syntheses or guidelines pooled it, 236 citations in OpenAlex.
- Unveiling sex-based differences in Parkinson's disease: a comprehensive meta-analysis of transcriptomic studies.Biology of sex differences · 2022Pooled it
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.Nature communications · 2025Trial
- Technologies to measure and modulate protein subcellular localization.Nature reviews. Molecular cell biology · 2026Review
- Article
- Targeting the integrated stress response or Ataxin-2 alleviates neurodegeneration in PolyGR models of C9orf72 associated frontotemporal dementia and amyotrophic lateral sclerosis.Acta neuropathologica communications · 2026Article
- The polygenic, omnigenic and stratagenic models of complex disease risk.Nature genetics · 2026Review
- CRISPR-based functional genomic screening in neurodegeneration: mechanistic insights into AD, PD, and ALS.Frontiers in aging neuroscience · 2026Review
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- Rigor & Reproducibility: pH Adjustments of Papain with L-Cysteine Dissociation Solutions and Cell Media Using Phenol Red Spectrophotometry.Biosensors · 2025Article
- Mutations in the Key Autophagy Tethering Factor EPG5 Link Neurodevelopmental and Neurodegenerative Disorders Including Early-Onset Parkinsonism.Annals of neurology · 2025Article
- The non-canonical thioreductase Tmx2b is essential for neuronal survival during zebrafish embryonic brain development.Development (Cambridge, England) · 2025Article
- Functional Neurogenomics to Dissect Disease Mechanisms Across Models.Annual review of genomics and human genetics · 2025Review
- Selenium Nanoparticles as Neuroprotective Agents: Insights into Molecular Mechanisms for Parkinson's Disease Treatment.Molecular neurobiology · 2025Review
- Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.Translational neurodegeneration · 2025Review
- 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
- Unlocking Disease-Modifying Treatments for TDP-43-Mediated Neurodegeneration.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- C9ORF72 poly-PR disrupts expression of ALS/FTD-implicated STMN2 through SRSF7.Acta neuropathologica communications · 2025Article
- Artificial enforcement of the unfolded protein response reduces disease features in multiple preclinical models of ALS/FTD.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
81 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases.
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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.