ArticleNeuron2021
Translation of GGC repeat expansions into a toxic polyglycine protein in NIID defines a novel class of human genetic disorders: The polyG diseases.
Article in Neuron, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- Advances of NOTCH2NLC Repeat Expansions and Associated Diseases: A Bibliometric and Meta-analysis.Molecular neurobiology · 2024Pooled it
- Structural Polymorphism of polyG Inclusions Revealed by In Situ Cryo-Electron Tomography.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Expanded Polyglycine Protein Aggregates Alter the RNA Splicing Profile into a Premature State Partially via Sequestering SF3B4.Neuroscience bulletin · 2026Article
- Distinctive hydrocephalus-like phenotype in NOTCH2NLC-related neuronal intranuclear inclusion disease: clinicopathological features and therapeutic implications.Acta neuropathologica communications · 2026Article
- Overflow urinary incontinence as an early manifestation of neuronal intranuclear inclusion disease (NIID): a case report.Journal of medical case reports · 2026Article
- ASO therapy rescues NOTCH2NLC GGC repeat expansion-induced genomic damage, 3D chromatin structural abnormalities, and senescence.Nature communications · 2026Article
- The Hsp40 cochaperone DNAJC7 regulates polyglutamine aggregation and exhibits context-dependent effects on polyglycine aggregation.The Journal of biological chemistry · 2026Article
- Pathogenic CGG expansions in oculopharyngodistal myopathy exhibit distinct characteristics of each causative gene on the flanking sequences as well as methylation status.Genome medicine · 2026Article
- Translation of expanded CGG repeats in LRP12 associated oculopharyngodistal myopathy.Acta neuropathologica communications · 2026Article
- The Tale of the Guanosine Tract in Repeat Expansion Disorders.Molecular neurobiology · 2026Review
- GGC repeat expansions within new open reading frames are translated into toxic polyglycine proteins in oculopharyngodistal myopathy.Nature genetics · 2026Article
- PML targets and resolves structured protein inclusions to mitigate neurodegeneration.Nature cell biology · 2026Article
- 'Non-coding' GGC repeats are translated into toxic polyglycine proteins in neuromuscular diseases.Nature genetics · 2026Article
- NOTCH2NLC GGC repeat expansions cause retinal neurodegeneration in neuronal intranuclear inclusion disease mouse model.Cell & bioscience · 2026Article
- Neuronal intranuclear inclusion disease: a diagnostic pitfall for MELAS.BMC neurology · 2026Article
- Lifetime risk of cancer in carriers of intermediate alleles in the HTT gene.Scientific reports · 2026Article
- Precise excision of expanded GGC repeats in NOTCH2NLC via CRISPR/Cas9 for treating neuronal intranuclear inclusion disease.Nature communications · 2026Article
- Immunological characterization of neuronal intranuclear inclusion disease with kidney injury: an exploratory analysis in a multi-center cohort.Frontiers in immunology · 2026Observational
- Evolutionary implications ofBrain communications · 2026Article
- Novel proteomics and neuropathology ofFrontiers in aging neuroscience · 2026Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 7 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by the presence of intranuclear inclusions of unknown origin. NIID is caused by an expansion of GGC repeats in the 5' UTR of the NOTCH2NLC (N2C) gene. We found that these repeats are embedded in a small upstream open reading frame (uORF) (uN2C), resulting in their translation into a polyglycine-containing protein, uN2CpolyG. This protein accumulates in intranuclear inclusions in cell and mouse models and in tissue samples of individuals with NIID. Furthermore, expression of uN2CpolyG in mice leads to locomotor alterations, neuronal cell loss, and premature death of the animals. These results suggest that translation of expanded GGC repeats into a novel and pathogenic polyglycine-containing protein underlies the presence of intranuclear inclusions and neurodegeneration in NIID.
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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.