ArticlePloS one2012
Aggregation of polyQ proteins is increased upon yeast aging and affected by Sir2 and Hsf1: novel quantitative biochemical and microscopic assays.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Scp160 deletion suppresses TDP-43 aggregation and toxicity inMicrobial cell (Graz, Austria) · 2026Article
- Accurate Quantification of Mutant and Wild-Type polyQ Proteins Using Simple Western Capillary Immunoassays.Molecular neurobiology · 2025Article
- Review
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- Vitamin B3 Biotech · 2023Article
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- Integrated multi-omics analysis of Huntington disease identifies pathways that modulate protein aggregation.Disease models & mechanisms · 2022Article
- Aggresome-Like Formation Promotes Resistance to Proteotoxicity in Cells from Long-Lived Species.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Article
- Article
- The yeast stress inducible Ssa Hsp70 reduces α-synuclein toxicity by promoting its degradation through autophagy.PLoS genetics · 2018Article
- Studying Spatial Protein Quality Control, Proteopathies, and Aging Using Different Model Misfolding Proteins inFrontiers in molecular neuroscience · 2018Review
- The copper transport-associated protein Ctr4 can form prion-like epigenetic determinants inMicrobial cell (Graz, Austria) · 2017Article
- Multiple discrete soluble aggregates influence polyglutamine toxicity in a Huntington's disease model system.Scientific reports · 2016Article
- Article
- Gpd1 Regulates the Activity of Tcp-1 and Heat Shock Response in Yeast Cells: Effect on Aggregation of Mutant Huntingtin.Molecular neurobiology · 2016Article
- Water-Transfer Slows Aging in Saccharomyces cerevisiae.PloS one · 2016Article
- Somatic expression of unc-54 and vha-6 mRNAs declines but not pan-neuronal rgef-1 and unc-119 expression in aging Caenorhabditis elegans.Scientific reports · 2015Article
- Ubiquitin-dependent proteolysis in yeast cells expressing neurotoxic proteins.Frontiers in molecular neuroscience · 2015Review
- Characterizing the altered cellular proteome induced by the stress-independent activation of heat shock factor 1.ACS chemical biology · 2014Article
- Yeast replicative aging: a paradigm for defining conserved longevity interventions.FEMS yeast research · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging-related neurodegenerative disorders, such as Parkinson's, Alzheimer's and Huntington's diseases, are characterized by accumulation of protein aggregates in distinct neuronal cells that eventually die. In Huntington's disease, the protein huntingtin forms aggregates, and the age of disease onset is inversely correlated to the length of the protein's poly-glutamine tract. Using quantitative assays to estimate microscopically and capture biochemically protein aggregates, here we study in Saccharomyces cerevisiae aging-related aggregation of GFP-tagged, huntingtin-derived proteins with different polyQ lengths. We find that the short 25Q protein never aggregates whereas the long 103Q version always aggregates. However, the mid-size 47Q protein is soluble in young logarithmically growing yeast but aggregates as the yeast cells enter the stationary phase and age, allowing us to plot an "aggregation timeline". This aging-dependent aggregation was associated with increased cytotoxicity. We also show that two aging-related genes, SIR2 and HSF1, affect aggregation of the polyQ proteins. In Δsir2 strain the aging-dependent aggregation of the 47Q protein is aggravated, while overexpression of the transcription factor Hsf1 attenuates aggregation. Thus, the mid-size 47Q protein and our quantitative aggregation assays provide valuable tools to unravel the roles of genes and environmental conditions that affect aging-related aggregation.
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Registered trials
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