ArticlePloS one2013
A powerful yeast model to investigate the synergistic interaction of α-synuclein and tau in neurodegeneration.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 38 citations in OpenAlex.
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- STIP1/HOP promotes the formation of cytotoxic α-synuclein oligomers.Molecular neurodegeneration advances · 2026Article
- From Yeast to Therapeutics: Modeling Neurodegenerative Diseases in Saccharomyces cerevisiae.Yeast (Chichester, England) · 2025Review
- Co-Expression of Mutant Tau and α-Synuclein in Neurons Promotes Tau Phosphorylation, Neuronal Loss, and Neuroinflammation in Mouse Brain.Molecular neurobiology · 2025Article
- Lewy body dementia: exploring biomarkers and pathogenic interactions of amyloid β, tau, and α-synuclein.Molecular neurodegeneration · 2025Review
- The Comorbidity of AD and PD: Exploring Clinical, Pathological, and Biomarker Interactions.Aging and disease · 2025Review
- Glucose starvation induces tau phosphorylation leading to cellular stress response in fission yeast.Archives of microbiology · 2025Article
- Effects of heterologous human tau protein expression in yeast models of proteotoxic stress response.CNS neuroscience & therapeutics · 2024Article
- The Vital Role of Melatonin and Its Metabolites in the Neuroprotection and Retardation of Brain Aging.International journal of molecular sciences · 2024Review
- Prevalence, distribution, and severity of cerebral amyloid angiopathy differ between Lewy body diseases and Alzheimer's disease.Acta neuropathologica communications · 2024Article
- Review
- The Aβ42 Peptide and IAPP Physically Interact in a Yeast-Based Assay.International journal of molecular sciences · 2023Article
- Alzheimer's Disease: Significant Benefit from the Yeast-Based Models.International journal of molecular sciences · 2023Review
- Interactions and Cytotoxicity of Human Neurodegeneration- Associated Proteins Tau and α-Synuclein in the Simple ModelFrontiers in cell and developmental biology · 2021Article
- Testing Amyloid Cross-Toxicity in the Vertebrate Brain.ACS omega · 2020Article
- Application of yeast to studying amyloid and prion diseases.Advances in genetics · 2020Review
- From Yeast to Humans: Leveraging New Approaches in Yeast to Accelerate Discovery of Therapeutic Targets for Synucleinopathies.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Neuroinflammation as a Common Feature of Neurodegenerative Disorders.Frontiers in pharmacology · 2019Review
- Protein Co-Aggregation Related to Amyloids: Methods of Investigation, Diversity, and Classification.International journal of molecular sciences · 2018Review
- Recent Insights on Alzheimer's Disease Originating from Yeast Models.International journal of molecular sciences · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several studies revealed consistent overlap between synucleinopathies and tauopathies, demonstrating that α-synuclein (ASYN) and tau co-localize in neurofibrillary tangles and in Lewy bodies from Alzheimer's and Parkinson's disease patients and corresponding animal models. Additionally, it has been shown that ASYN can act as an initiator of tau aggregation and phosphorylation and that these two proteins directly interact. Despite these evidences, the cellular pathway implicated in this synergistic interaction remains to be clarified. The aim of this study was to create a yeast model where the concomitant expression of ASYN and tau can be used to perform genome wide screenings for the identification of genes that modulate this interaction, in order to shed light into the pathological mechanism of cell dysfunction and to provide new targets for future therapeutic intervention. We started by validating the synergistic toxicity of tau and ASYN co-expression in yeast, by developing episomal and integrative strains expressing WT and mutant forms of both proteins, alone or in combination. The episomal strains showed no differences in growth delay upon expression of ASYN isoforms (WT or A53T) alone or in combination with tau 2N/4R isoforms (WT or P301L). However, in these strains, the presence of ASYN led to increased tau insolubility and correlated with increased tau phosphorylation in S396/404, which is mainly mediated by RIM11, the human homolog of GSK3β in yeast. On the other hand, the integrative strains showed a strong synergistic toxic effect upon co-expression of ASYN WT and tau WT, which was related to high levels of intracellular ASYN inclusions and increased tau phosphorylation and aggregation. Taken together, the strains described in the present study are able to mimic relevant pathogenic features involved in neurodegeneration and are powerful tools to identify potential target genes able to modulate the synergistic pathway driven by ASYN and tau interaction.
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.