ArticleThe Journal of biological chemistry2015
Truncation and Activation of Dual Specificity Tyrosine Phosphorylation-regulated Kinase 1A by Calpain I: A MOLECULAR MECHANISM LINKED TO TAU PATHOLOGY IN ALZHEIMER DISEASE.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Calcium signaling hypothesis: A non-negligible pathogenesis in Alzheimer's disease.Journal of advanced research · 2025Review
- Cholinotrophic basal forebrain connectome dysfunction in Down syndrome with and without dementia.iScience · 2025Article
- Expression profiles of the Tau-associated genesOpen veterinary journal · 2025Article
- DYRK1A in the physiology and pathology of the neuron-astrocyte axis.Frontiers in neuroscience · 2025Review
- Mitigating neuroinflammation in cognitive areas: exploring the impact of HMG-CoA reductase inhibitor.The Biochemical journal · 2024Article
- Truncated Dyrk1A aggravates neuronal apoptosis by inhibiting ASF-mediated Bcl-x exon 2b inclusion.CNS neuroscience & therapeutics · 2024Article
- Increased plasma DYRK1A with aging may protect against neurodegenerative diseases.Translational psychiatry · 2023Article
- Multilayered Networks of SalmoNet2 Enable Strain Comparisons of the Salmonella Genus on a Molecular Level.mSystems · 2022Article
- Article
- The chromosome 21 kinase DYRK1A: emerging roles in cancer biology and potential as a therapeutic target.Oncogene · 2022Review
- Application of a High-Throughput Targeted Sequence AmpliSeq Procedure to Assess the Presence and Variants of Virulence Genes inMicroorganisms · 2022Article
- Review
- Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview.International journal of molecular sciences · 2021Review
- DYRK1A: a down syndrome-related dual protein kinase with a versatile role in tumorigenesis.Cellular and molecular life sciences : CMLS · 2021Review
- Tau in Alzheimer's Disease: Pathological Alterations and an Attractive Therapeutic Target.Current medical science · 2020Review
- Neuronal overexpression of Alzheimer's disease and Down's syndrome associated DYRK1A/minibrain gene alters motor decline, neurodegeneration and synaptic plasticity in Drosophila.Neurobiology of disease · 2019Article
- A comprehensive proteomics-based interaction screen that links DYRK1A to RNF169 and to the DNA damage response.Scientific reports · 2019Article
- Inhibition of DYRK1A proteolysis modifies its kinase specificity and rescues Alzheimer phenotype in APP/PS1 mice.Acta neuropathologica communications · 2019Article
- Subacute to chronic Alzheimer-like alterations after controlled cortical impact in human tau transgenic mice.Scientific reports · 2019Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Hyperphosphorylation and dysregulation of exon 10 splicing of Tau are pivotally involved in pathogenesis of Alzheimer disease (AD) and/or other tauopathies. Alternative splicing of Tau exon 10, which encodes the second microtubule-binding repeat, generates Tau isoforms containing three and four microtubule-binding repeats, termed 3R-Taus and 4R-Taus, respectively. Dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A) lies at the Down syndrome critical region of chromosome 21. Overexpression of this kinase may contribute to the early Tau pathology in Down syndrome via phosphorylation of Tau and dysregulation of Tau exon 10. Here, we report that Dyrk1A was truncated at the C terminus and was associated with overactivation of calpain I in AD brain. Calpain I proteolyzed Dyrk1A in vitro first at the C terminus and further at the N terminus and enhanced its kinase activity toward Tau via increased Vmax but not Km. C-terminal truncation of Dyrk1A resulted in stronger activity than its full-length protein in promotion of exon 10 exclusion and phosphorylation of Tau. Dyrk1A was truncated in kainic acid-induced excitotoxic mouse brains and coincided with an increase in 3R-Tau expression and phosphorylation of Tau via calpain activation. Moreover, truncation of Dyrk1A was correlated with an increase in the ratio of 3R-Tau/4R-Tau and Tau hyperphosphorylation in AD brain. Collectively, these findings suggest that truncation/activation of Dyrk1A by Ca(2+)/calpain I might contribute to Tau pathology via promotion of exon 10 exclusion and hyperphosphorylation of Tau in AD brain.
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