ArticleAging cell2019
α-Synuclein toxicity in yeast and human cells is caused by cell cycle re-entry and autophagy degradation of ribonucleotide reductase 1.
Article in Aging cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- CORO1C (coronin 1C) promotes autophagosome formation by coordinating branched actin network dynamics.Autophagy · 2026Article
- Mutational Scanning of α-Synuclein using a Clickable Protein Tag Reveals Determinants of Membrane-Induced Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Concentration-dependent mutational scanning probes the cellular folding landscape of α-synuclein in yeast.Protein science : a publication of the Protein Society · 2026Article
- Concentration-Dependent Mutational Scanning Probes the Cellular Folding Landscape of α-Synuclein in Yeast.bioRxiv : the preprint server for biology · 2025Article
- Aberrant accumulation of phosphorylated BRCA1 in brainstem-type and cortical-type Lewy bodies in Lewy body disease.Journal of neuropathology and experimental neurology · 2025Article
- Biological Amyloids Chemically Damage DNA.ACS chemical neuroscience · 2025Article
- Nuclear Alpha-Synuclein in Parkinson's Disease and the Malignant Transformation in Melanoma.Neurology research international · 2025Article
- Exploring Influence of Production Area and Harvest Time on Specialized Metabolite Content ofAntioxidants (Basel, Switzerland) · 2024Article
- Targeting protein aggregation using a cocoa-bean shell extract to reduce α-synuclein toxicity in models of Parkinson's disease.Current research in food science · 2024Article
- Cdk5 and aberrant cell cycle activation at the core of neurodegeneration.Neural regeneration research · 2023Review
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Anti-Aging and Neuroprotective Properties ofNutrients · 2022Article
- Yeast as a Model to Find New Drugs and Drug Targets forInternational journal of molecular sciences · 2022Review
- Diterpene glycosides from Holothuria scabra exert the α-synuclein degradation and neuroprotection against α-synuclein-Mediated neurodegeneration in C. elegans model.Journal of ethnopharmacology · 2021Article
- α-Synuclein Decreases the Abundance of Proteasome Subunits and Alters Ubiquitin Conjugates in Yeast.Cells · 2021Article
- Comprehensive miRNome-Wide Profiling in a Neuronal Cell Model of Synucleinopathy Implies Involvement of Cell Cycle Genes.Frontiers in cell and developmental biology · 2021Article
- A multi-faceted genotoxic network of alpha-synuclein in the nucleus and mitochondria of dopaminergic neurons in Parkinson's disease: Emerging concepts and challenges.Progress in neurobiology · 2020Review
- Vitamin D, gut microbiota, and radiation-related resistance: a love-hate triangle.Journal of experimental & clinical cancer research : CR · 2019Review
- α-Synuclein toxicity in yeast and human cells is caused by cell cycle re-entry and autophagy degradation of ribonucleotide reductase 1.Aging cell · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
α-Synuclein (aSyn) toxicity is associated with cell cycle alterations, activation of DNA damage responses (DDR), and deregulation of autophagy. However, the relationships between these phenomena remain largely unknown. Here, we demonstrate that in a yeast model of aSyn toxicity and aging, aSyn expression induces Ras2-dependent growth signaling, cell cycle re-entry, DDR activation, autophagy, and autophagic degradation of ribonucleotide reductase 1 (Rnr1), a protein required for the activity of ribonucleotide reductase and dNTP synthesis. These events lead to cell death and aging, which are abrogated by deleting RAS2, inhibiting DDR or autophagy, or overexpressing RNR1. aSyn expression in human H4 neuroglioma cells also induces cell cycle re-entry and S-phase arrest, autophagy, and degradation of RRM1, the human homologue of RNR1, and inhibiting autophagic degradation of RRM1 rescues cells from cell death. Our findings represent a model for aSyn toxicity that has important implications for understanding synucleinopathies and other age-related neurodegenerative diseases.
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