ArticleHuman molecular genetics2016
Inhibition of death-associated protein kinase 1 attenuates the phosphorylation and amyloidogenic processing of amyloid precursor protein.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 4 of them syntheses that pooled it.
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Who cites it
44 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Extracellular Vesicle-Derived microRNAs as Fluid Biomarkers in Neurodegenerative Diseases: A Systematic Review.Journal of neurochemistry · 2026Pooled it
- A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores.Molecular neurodegeneration · 2023Pooled it
- Genome-wide association study of brain amyloid deposition as measured by Pittsburgh Compound-B (PiB)-PET imaging.Molecular psychiatry · 2021Pooled it
- Revealing a Novel Landscape of the Association Between Blood Lipid Levels and Alzheimer's Disease: A Meta-Analysis of a Case-Control Study.Frontiers in aging neuroscience · 2019Pooled it
- Development of a Novel AAV-Mediated microRNA Gene Therapy for Spatial Suppression of BACE1 to Improve Cognitive Function in Alzheimer's Disease Model Mice.Biomolecules · 2026Article
- MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.Neural regeneration research · 2026Article
- Crosstalk between death-associated protein kinase 1-regulated mechanisms and dysfunctions in alzheimer's disease.Molecular biology reports · 2026Review
- A Novel PROTAC Confers a Dual Benefit Against Amyloid and Tau Pathology in Alzheimer's Disease via DAPK1 Degradation.International journal of biological sciences · 2026Article
- Aβ Modulates Extracellular Vesicles Proteomic Profile Impacting Phosphorylation Mediators.Molecular neurobiology · 2025Article
- Death-associated protein kinase 1-dependent SENP1 degradation increases tau SUMOylation and leads to cognitive dysfunction in a mouse model for tauopathy.Molecular neurodegeneration · 2025Article
- APP SUMOylation prevents BACE1 cleavage of APP and increases BACE1 degradation to promote the nonamyloidogenic pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- Protein modification in neurodegenerative diseases.MedComm · 2024Review
- Mechanism of DAPK1 for Regulating Cancer Stem Cells in Thyroid Cancer.Current issues in molecular biology · 2024Review
- Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease.Translational neurodegeneration · 2024Review
- Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer-like neuropathology in 5×FAD mice.Frontiers in pharmacology · 2024Article
- Article
- Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach.International journal of molecular sciences · 2023Review
- Potential Implications of miRNAs in the Pathogenesis, Diagnosis, and Therapeutics of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Beta-Secretase 1 Recruits Amyloid-Beta Precursor Protein to ROCK2 Kinase, Resulting in Erroneous Phosphorylation and Beta-Amyloid Plaque Formation.International journal of molecular sciences · 2023Article
- Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Extracellular deposition of amyloid-beta (Aβ) peptide, a metabolite of sequential cleavage of amyloid precursor protein (APP), is a critical step in the pathogenesis of Alzheimer's disease (AD). While death-associated protein kinase 1 (DAPK1) is highly expressed in AD brains and its genetic variants are linked to AD risk, little is known about the impact of DAPK1 on APP metabolism and Aβ generation. In this study, we demonstrated a novel effect of DAPK1 in the regulation of APP processing using cell culture and mouse models. DAPK1, but not its kinase deficient mutant (K42A), significantly increased human Aβ secretion in neuronal cell culture models. Moreover, knockdown of DAPK1 expression or inhibition of DAPK1 catalytic activity significantly decreased Aβ secretion. Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of Aβ. In Tg2576 APPswe-overexpressing mice, knockout of DAPK1 shifted APP processing toward non-amyloidogenic pathway and decreased Aβ generation. Finally, in AD brains, elevated DAPK1 levels showed co-relation with the increase of APP phosphorylation. Combined together, these results suggest that DAPK1 promotes the phosphorylation and amyloidogenic processing of APP, and that may serve a potential therapeutic target for AD.
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