Abstract
Small molecules with antioxidative properties have been implicated in amyloid disorders. Curcumin is the active ingredient present in turmeric and known for several biological and medicinal effects. Adequate evidence substantiates the importance of curcumin in Alzheimer's disease and recent evidence suggests its role in Prion and Parkinson's disease. However, contradictory effects have been suggested for Huntington's disease. This difference provided a compelling reason to investigate the effect of curcumin on glutamine-rich (Q-rich) and non-glutamine-rich (non Q-rich) amyloid aggregates in the well established yeast model system. Curcumin significantly inhibited the formation of htt72Q-GFP (a Q-rich) and Het-s-GFP (a non Q-rich) aggregates in yeast. We show that curcumin prevents htt72Q-GFP aggregation by down regulating Vps36, a component of the ESCRT-II (Endosomal sorting complex required for transport). Moreover, curcumin disrupted the htt72Q-GFP aggregates that were pre-formed in yeast and cured the yeast prion, [PSI(+)].
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphatases / metabolism
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Ascorbic Acid / pharmacology
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Curcumin / pharmacology*
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Endosomal Sorting Complexes Required for Transport / antagonists & inhibitors*
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Endosomal Sorting Complexes Required for Transport / metabolism
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Flavonoids / pharmacology
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Gene Deletion
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Green Fluorescent Proteins / metabolism
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Humans
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Peptides / chemistry*
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Peptides / metabolism*
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Protein Stability / drug effects
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Protein Structure, Quaternary
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Saccharomyces cerevisiae / cytology
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / antagonists & inhibitors*
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Saccharomyces cerevisiae Proteins / metabolism
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alpha-Tocopherol / pharmacology
Substances
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Endosomal Sorting Complexes Required for Transport
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Flavonoids
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Peptides
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Saccharomyces cerevisiae Proteins
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VPS4 protein, S cerevisiae
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Vps36 protein, S cerevisiae
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Green Fluorescent Proteins
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polyglutamine
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morin
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Adenosine Triphosphatases
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alpha-Tocopherol
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Curcumin
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Ascorbic Acid
Grants and funding
Innovative Young Biotechnology Award, Department of Biotechnology, Government of India, India. VT acknowledges fellowship from Innovative Young Biotechnologist Award, Department of Biotechnology, India. MV acknowledges senior research fellowship from Indian Council of Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.