ArticleJournal of pineal research2020
Melatonin directly binds and inhibits death-associated protein kinase 1 function in Alzheimer's disease.
Article in Journal of pineal research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Selective degradation of DAPK1 via a novel hydrophobic tagging attenuates tau pathology in Alzheimer's disease.Journal of advanced research · 2026Article
- Crosstalk between death-associated protein kinase 1-regulated mechanisms and dysfunctions in alzheimer's disease.Molecular biology reports · 2026Review
- Zipper-interacting Protein Kinase Modulates Gene Expression Linked to Synaptic and Neuronal Processes after Traumatic Brain Injury.Molecular neurobiology · 2026Article
- 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
- 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
- Linkage of circadian rhythm disruptions with Alzheimer's disease and therapeutic interventions.Acta pharmaceutica Sinica. B · 2025Review
- Zipper-interacting protein kinase mediates neuronal cell death and cognitive dysfunction in traumatic brain injury via regulating DEDD.Cell death & disease · 2025Article
- Food Functional Factors in Alzheimer's Disease Intervention: Current Research Progress.Nutrients · 2024Review
- Protective Activity of Melatonin Combinations and Melatonin-Based Hybrid Molecules in Neurodegenerative Diseases.Journal of pineal research · 2024Review
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- Review
- Activation of transient receptor potential vanilloid 1 ameliorates tau accumulation-induced synaptic damage and cognitive dysfunction via autophagy enhancement.CNS neuroscience & therapeutics · 2024Article
- Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease.Translational neurodegeneration · 2024Review
- Article
- Death-associated protein kinase 1 phosphorylates MDM2 and inhibits its protein stability and function.Archives of pharmacal research · 2023Article
- Ablation of Death-Associated Protein Kinase 1 Changes the Transcriptomic Profile and Alters Neural-Related Pathways in the Brain.International journal of molecular sciences · 2023Article
- Electroacupuncture ameliorates cerebrovascular impairment in Alzheimer's disease mice via melatonin signaling.CNS neuroscience & therapeutics · 2023Article
- Article
- Multi-Targeting Intranasal Nanoformulation as a Therapeutic for Alzheimer's Disease.Biomolecules · 2023Article
- Therapeutics of Alzheimer's Disease: Recent Developments.Antioxidants (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Death-associated protein kinase 1 (DAPK1) is upregulated in the brains of human Alzheimer's disease (AD) patients compared with normal subjects, and aberrant DAPK1 regulation is implicated in the development of AD. However, little is known about whether and how DAPK1 function is regulated in AD. Here, we identified melatonin as a critical regulator of DAPK1 levels and function. Melatonin significantly decreases DAPK1 expression in a post-transcriptional manner in neuronal cell lines and mouse primary cortical neurons. Moreover, melatonin directly binds to DAPK1 and promotes its ubiquitination, resulting in increased DAPK1 protein degradation through a proteasome-dependent pathway. Furthermore, in tau-overexpressing mouse brain slices, melatonin treatment and the inhibition of DAPK1 kinase activity synergistically decrease tau phosphorylation at multiple sites related to AD. In addition, melatonin and DAPK1 inhibitor dramatically accelerate neurite outgrowth and increase the assembly of microtubules. Mechanistically, melatonin-mediated DAPK1 degradation increases the activity of Pin1, a prolyl isomerase known to play a protective role against tau hyperphosphorylation and tau-related pathologies. Finally, elevated DAPK1 expression shows a strong correlation with the decrease in melatonin levels in human AD brains. Combined, these results suggest that DAPK1 regulation by melatonin is a novel mechanism that controls tau phosphorylation and function and offers new therapeutic options for treating human AD.
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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.