ArticleHuman molecular genetics2009
Dissociation of tau toxicity and phosphorylation: role of GSK-3beta, MARK and Cdk5 in a Drosophila model.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
87 citing papers in PubMed, 175 citations in OpenAlex.
- MARK4 enhances stress granule formation under oxidative stress and increases tau accumulation.FEBS open bio · 2026Article
- Systems genetic dissection of brain gene expression reveals excitotoxic mechanisms of Alzheimer's disease.Molecular psychiatry · 2026Article
- The Bright and Dark Sides of Nitric Oxide in Neurodegenerative Diseases.Journal of personalized medicine · 2026Review
- 5-ALA/SFC Mitigates Tau Toxicity via Lowering Oxidative Stress in aLife (Basel, Switzerland) · 2026Article
- Protein kinases as therapeutic targets in Alzheimer's disease: challenges, insights, and new frontiers.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- GSK-3β coordinates axonal microtubule organization through Shot and Tau.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Drosophila wing is a high-throughput and versatile screening tool for Tau-mediated disease mechanisms and drug discovery.Disease models & mechanisms · 2026Article
- Revealing the nervous system requirements of Alzheimer disease risk genes in Drosophila.American journal of human genetics · 2025Article
- Evaluation of the toxicity and efficacy of a multi-target polymer-drug nano-polyplex in SH-SY5Y cells and Drosophila model of tauopathy.Scientific reports · 2025Article
- Human Glucose Transporters in Health and Selected Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Revealing the nervous system requirements of Alzheimer's disease risk genes inbioRxiv : the preprint server for biology · 2025Article
- Neuronal glycogen breakdown mitigates tauopathy via pentose-phosphate-pathway-mediated oxidative stress reduction.Nature metabolism · 2025Article
- Associations Between Diabetes Mellitus and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer's disease and other tauopathies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Mendelian Randomization Identifies Genetically Supported Drug Targets for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Molecular neurobiology · 2024Article
- Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK.Cell metabolism · 2024Article
- Microtubule-affinity regulating kinase family members distinctively affect tau phosphorylation and promote its toxicity in a Drosophila model.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Quantitative live cell imaging of a tauopathy model enables the identification of a polypharmacological drug candidate that restores physiological microtubule interaction.Nature communications · 2024Article
- Identification of Tau Toxicity Modifiers in the Drosophila Eye.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Hyperphosphorylation of tau at multiple sites has been implicated in the formation of neurofibrillary tangles in Alzheimer's disease; however, the relationship between toxicity and phosphorylation of tau has not been clearly elucidated. Putative tau kinases that play a role in such phosphorylation events include the proline-directed kinases glycogen synthase kinase-3beta (GSK-3beta) and cyclin-dependent kinase 5 (Cdk5), as well as nonproline-directed kinases such as microtubule affinity-regulating kinase (MARK)/PAR-1; however, whether the cascade of events linking tau phosphorylation and neurodegeneration involves sequential action of kinases as opposed to parallel pathways is still a matter of controversy. Here, we employed a well-characterized Drosophila model of tauopathy to investigate the interdependence of tau kinases in regulating the phosphorylation and toxicity of tau in vivo. We found that tau mutants resistant to phosphorylation by MARK/PAR-1 were indeed less toxic than wild-type tau; however, this was not due to their resistance to phosphorylation by GSK-3beta/Shaggy. On the contrary, a tau mutant resistant to phosphorylation by GSK-3beta/Shaggy retained substantial toxicity and was found to have increased affinity for microtubules compared with wild-type tau. The fly homologs of Cdk5/p35 did not have major effects on tau toxicity or phosphorylation in this model. These data suggest that, in addition to tau phosphorylation, microtubule binding plays a crucial role in the regulation of tau toxicity when misexpressed. These data have important implications for the understanding and interpretation of animal models of tauopathy.
Indexed as
Identifiers
What OpenQuestion holds
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.