ArticleHuman molecular genetics2015
A new model to study neurodegeneration in ataxia oculomotor apraxia type 2.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Ataxia with oculomotor apraxia type 2 due to the new compound heterozygous variants c.5825T>C (inherited) and c.6106+1G>T (de novo) in SETX.Clinics (Sao Paulo, Brazil) · 2026Article
- The SMC5/SMC6 complex is critical for resolving R-loop-induced transcription-replication conflicts.Nucleic acids research · 2026Article
- MIXL1 activation in endoderm differentiation of human induced pluripotent stem cells.Stem cell reports · 2025Article
- Mechanisms underlining R-loop biology and implications for human disease.Frontiers in cell and developmental biology · 2025Review
- How do neurons live long and healthy? The mechanism of neuronal genome integrity.Frontiers in neuroscience · 2025Review
- Senataxin deficiency disrupts proteostasis through nucleolar ncRNA-driven protein aggregation.The Journal of cell biology · 2024Article
- R-loop and diseases: the cell cycle matters.Molecular cancer · 2024Review
- Role of senataxin in R-loop-mediated neurodegeneration.Brain communications · 2024Review
- Human senataxin is a bona fide R-loop resolving enzyme and transcription termination factor.Nucleic acids research · 2023Article
- DNA damage and repair in age-related inflammation.Nature reviews. Immunology · 2023Review
- TERRA beyond cancer: the biology of telomeric repeat-containing RNAs in somatic and germ cells.Frontiers in aging · 2023Review
- Flap Endonuclease 1 Endonucleolytically Processes RNA to Resolve R-Loops through DNA Base Excision Repair.Genes · 2022Article
- Review
- Tissue-Specific, Genome-wide Mapping of R-loops inBio-protocol · 2022Article
- Mutation in senataxin alters the mechanism of R-loop resolution in amyotrophic lateral sclerosis 4.Brain : a journal of neurology · 2022Article
- Sources, resolution and physiological relevance of R-loops and RNA-DNA hybrids.Nature reviews. Molecular cell biology · 2022Review
- Walking a tightrope: The complex balancing act of R-loops in genome stability.Molecular cell · 2022Review
- Integrated genome and transcriptome analyses reveal the mechanism of genome instability in ataxia with oculomotor apraxia 2.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- R-loop Mediated DNA Damage and Impaired DNA Repair in Spinal Muscular Atrophy.Frontiers in cellular neuroscience · 2022Review
- Regulating autophagy: a novel role for SETX (Senataxin).Neural regeneration research · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
Ataxia oculomotor apraxia type 2 (AOA2) is a rare autosomal recessive cerebellar ataxia. Recent evidence suggests that the protein defective in this syndrome, senataxin (SETX), functions in RNA processing to protect the integrity of the genome. To date, only patient-derived lymphoblastoid cells, fibroblasts and SETX knockdown cells were available to investigate AOA2. Recent disruption of the Setx gene in mice did not lead to neurobehavioral defects or neurodegeneration, making it difficult to study the etiology of AOA2. To develop a more relevant neuronal model to study neurodegeneration in AOA2, we derived neural progenitors from a patient with AOA2 and a control by induced pluripotent stem cell (iPSC) reprogramming of fibroblasts. AOA2 iPSC and neural progenitors exhibit increased levels of oxidative damage, DNA double-strand breaks, increased DNA damage-induced cell death and R-loop accumulation. Genome-wide expression and weighted gene co-expression network analysis in these neural progenitors identified both previously reported and novel affected genes and cellular pathways associated with senataxin dysfunction and the pathophysiology of AOA2, providing further insight into the role of senataxin in regulating gene expression on a genome-wide scale. These data show that iPSCs can be generated from patients with the autosomal recessive ataxia, AOA2, differentiated into neurons, and that both cell types recapitulate the AOA2 cellular phenotype. This represents a novel and appropriate model system to investigate neurodegeneration in this syndrome.
Indexed as
Identifiers
What OpenQuestion holds
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.