ArticleActa neuropathologica communications2019
Drosophila Ref1/ALYREF regulates transcription and toxicity associated with ALS/FTD disease etiologies.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Phototriggered Morphological and Compositional Change of UGGAA Repeat RNA Foci by Photoswitchable RNA-Binding Ligand.Angewandte Chemie (International ed. in English) · 2026Article
- TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models.The FEBS journal · 2026Review
- eVGeMdb: a manually curated database for experimentally validated genetic modifiers of neurodegenerative disorders.NAR molecular medicine · 2026Article
- Exploring the versatility ofFly · 2025Review
- Identifying dysregulated regions in amyotrophic lateral sclerosis through chromatin accessibility outliers.HGG advances · 2024Article
- Article
- Review
- HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS.Acta neuropathologica · 2022Article
- Heat shock protein Grp78/BiP/HspA5 binds directly to TDP-43 and mitigates toxicity associated with disease pathology.Scientific reports · 2022Article
- Loss of aly/ALYREF suppresses toxicity in both tau and TDP-43 models of neurodegeneration.GeroScience · 2022Article
- Fly for ALS: Drosophila modeling on the route to amyotrophic lateral sclerosis modifiers.Cellular and molecular life sciences : CMLS · 2021Review
- Triad of TDP43 control in neurodegeneration: autoregulation, localization and aggregation.Nature reviews. Neuroscience · 2021Review
- RNA dependent suppression of C9orf72 ALS/FTD associated neurodegeneration by Matrin-3.Acta neuropathologica communications · 2020Article
- Quality-control mechanisms targeting translationally stalled and C-terminally extended poly(GR) associated with ALS/FTD.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Altered MICOS Morphology and Mitochondrial Ion Homeostasis Contribute to Poly(GR) Toxicity Associated with C9-ALS/FTD.Cell reports · 2020Article
- Alcohol Causes Lasting Differential Transcription inGenetics · 2020Article
- Modeling Neurodegenerative Disorders inInternational journal of molecular sciences · 2020Review
- The Role of Lozenge inMolecules and cells · 2020Review
- Genome wide analysis reveals heparan sulfate epimerase modulates TDP-43 proteinopathy.PLoS genetics · 2019Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
RNA-binding proteins (RBPs) are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the underlying disease mechanisms remain unclear. In an unbiased screen in Drosophila for RBPs that genetically interact with TDP-43, we found that downregulation of the mRNA export factor Ref1 (fly orthologue to human ALYREF) mitigated TDP-43 induced toxicity. Further, Ref1 depletion also reduced toxicity caused by expression of the C9orf72 GGGGCC repeat expansion. Ref1 knockdown lowered the mRNA levels for these related disease genes and reduced the encoded proteins with no effect on a wild-type Tau disease transgene or a control transgene. Interestingly, expression of TDP-43 or the GGGGCC repeat expansion increased endogenous Ref1 mRNA levels in the fly brain. Further, the human orthologue ALYREF was upregulated by immunohistochemistry in ALS motor neurons, with the strongest upregulation occurring in ALS cases harboring the GGGGCC expansion in C9orf72. These data support ALYREF as a contributor to ALS/FTD and highlight its downregulation as a potential therapeutic target that may affect co-existing disease etiologies.
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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 Socratic graph.