ArticleActa neuropathologica communications2019
Inhibition of DYRK1A proteolysis modifies its kinase specificity and rescues Alzheimer phenotype in APP/PS1 mice.
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 22 papers.
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Who cites it
22 citing papers in PubMed, 46 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
- Pharmacokinetics, distribution, metabolism, excretion and safety characterization of ZJCK-6-72: novel DYRK1A inhibitor with optimized brain exposure for Alzheimer's disease therapy.Frontiers in pharmacology · 2026Article
- Targeting dual specificity tyrosine-phosphorylation-regulated kinase 1A mitigates tauopathy and enhances recovery after repetitive head injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Unlocking the Therapeutic Potential of the Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitors in Alzheimer's Diseases.Molecular neurobiology · 2025Review
- DYRK1A in the physiology and pathology of the neuron-astrocyte axis.Frontiers in neuroscience · 2025Review
- Discovering a novel dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) inhibitor and its impact on tau phosphorylation and amyloid-β formation.Journal of enzyme inhibition and medicinal chemistry · 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
- Truncated Dyrk1A aggravates neuronal apoptosis by inhibiting ASF-mediated Bcl-x exon 2b inclusion.CNS neuroscience & therapeutics · 2024Article
- Development of Novel Fluorinated Polyphenols as Selective Inhibitors of DYRK1A/B Kinase for Treatment of Neuroinflammatory Diseases including Parkinson's Disease.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Article
- Type 2 Diabetes Mellitus and Alzheimer's Disease: Shared Molecular Mechanisms and Potential Common Therapeutic Targets.International journal of molecular sciences · 2022Review
- Article
- Catechins as a Potential Dietary Supplementation in Prevention of Comorbidities Linked with Down Syndrome.Nutrients · 2022Review
- Review
- Diabetic Kinome Inhibitors-A New Opportunity for β-Cells Restoration.International journal of molecular sciences · 2021Review
- 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
- GLUT12 Expression in Brain of Mouse Models of Alzheimer's Disease.Molecular neurobiology · 2020Article
- [Molecules (Basel, Switzerland) · 2019Article
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent evidences suggest the involvement of DYRK1A (dual specificity tyrosine phosphorylation-regulated kinase 1 A) in Alzheimer's disease (AD). Here we showed that DYRK1A undergoes a proteolytic processing in AD patients hippocampus without consequences on its kinase activity. Resulting truncated forms accumulate in astrocytes and exhibit increased affinity towards STAT3ɑ, a regulator of inflammatory process. These findings were confirmed in APP/PS1 mice, an amyloid model of AD, suggesting that this DYRK1A cleavage is a consequence of the amyloid pathology. We identified in vitro the Leucettine L41 as a compound able to prevent DYRK1A proteolysis in both human and mouse protein extracts. We then showed that intraperitoneal injections of L41 in aged APP/PS1 mice inhibit STAT3ɑ phosphorylation and reduce pro-inflammatory cytokines levels (IL1- β, TNF-ɑ and IL-12) associated to an increased microglial recruitment around amyloid plaques and decreased amyloid-β plaque burden. Importantly, L41 treatment improved synaptic plasticity and rescued memory functions in APP/PS1 mice. Collectively, our results suggest that DYRK1A may contribute to AD pathology through its proteolytic process, reducing its kinase specificity. Further evaluation of inhibitors of DYRK1A truncation promises a new therapeutic approach for AD.
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