ArticleThe Journal of biological chemistry2008
Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 171 citations in OpenAlex.
- Elevated DYRK1A in Primary Tauopathies and Therapeutic Targeting with the Brain-Penetrant Inhibitor DYR533.Research square · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Epigenetic treatment of synaptic and behavioral deficits in Dyrk1a-mutant mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Decoding SR protein regulation: kinases, phosphatases, and therapeutic targeting strategies.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- ZDWX-25, a dual DYRK1A/GSK3β inhibitor, attenuates tau hyperphosphorylation and neuroinflammation in acute mouse models.Frontiers in pharmacology · 2026Article
- Exploring peripheral fluid biomarkers for early detection of Alzheimer's disease in Down syndrome: A literature review.Heliyon · 2025Review
- DYRK1A roles in human neural progenitors.Frontiers in neuroscience · 2025Article
- DYRK1A in the physiology and pathology of the neuron-astrocyte axis.Frontiers in neuroscience · 2025Review
- Article
- Regulatory interplay between SR proteins governsRNA (New York, N.Y.) · 2024Article
- Cryo-EM structures reveal tau filaments from Down syndrome adopt Alzheimer's disease fold.Acta neuropathologica communications · 2024Article
- Genetic forms of tauopathies: inherited causes and implications of Alzheimer's disease-like TAU pathology in primary and secondary tauopathies.Journal of neurology · 2024Review
- Psychoplastogenic DYRK1A Inhibitors with Therapeutic Effects Relevant to Alzheimer's Disease.Journal of medicinal chemistry · 2024Article
- An in vitro neurogenetics platform for precision disease modeling in the mouse.Science advances · 2024Article
- Truncated Dyrk1A aggravates neuronal apoptosis by inhibiting ASF-mediated Bcl-x exon 2b inclusion.CNS neuroscience & therapeutics · 2024Article
- Increased dosage of DYRK1A leads to congenital heart defects in a mouse model of Down syndrome.Science translational medicine · 2024Article
- Towards understandings of serine/arginine-rich splicing factors.Acta pharmaceutica Sinica. B · 2023Review
- Therapeutic Targeting of RNA Splicing in Cancer.Genes · 2023Review
- Urolithin A exhibits a neuroprotective effect against Alzheimer's disease by inhibiting DYRK1A activity.Journal of food and drug analysis · 2023Article
- Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors.Life (Basel, Switzerland) · 2023Review
35 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Two groups of tau, 3R- and 4R-tau, are generated by alternative splicing of tau exon 10. Normal adult human brain expresses equal levels of them. Disruption of the physiological balance is a common feature of several tauopathies. Very early in their life, individuals with Down syndrome (DS) develop Alzheimer-type tau pathology, the molecular basis for which is not fully understood. Here, we demonstrate that Dyrk1A, a kinase encoded by a gene in the DS critical region, phosphorylates alternative splicing factor (ASF) at Ser-227, Ser-234, and Ser-238, driving it into nuclear speckles and preventing it from facilitating tau exon 10 inclusion. The increased dosage of Dyrk1A in DS brain due to trisomy of chromosome 21 correlates to an increase in 3R-tau level, which on abnormal hyperphosphorylation and aggregation of tau results in neurofibrillary degeneration. Imbalance of 3R- and 4R-tau in DS brain by Dyrk1A-induced dysregulation of alternative splicing factor-mediated alternative splicing of tau exon 10 represents a novel mechanism of neurofibrillary degeneration and may help explain early onset tauopathy in individuals with DS.
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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.