title: Curcumin prevents formation of polyglutamine aggregates by inhibiting Vps36, a component of the ESCRT-II complex.
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(+)].
authors.affiliation: Genomics and Molecular Medicine, Institute of Genomics and Integrative Biology, Mall Road, Delhi, India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Verma
authors.forename: Abhishek
authors.initials: A
authors.lastname: Sharma
authors.forename: Swarna
authors.initials: S
authors.lastname: Naidu
authors.forename: Ankan Kumar
authors.initials: AK
authors.lastname: Bhadra
authors.forename: Ritushree
authors.initials: R
authors.lastname: Kukreti
authors.forename: Vibha
authors.initials: V
authors.lastname: Taneja
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D055550:Protein Stability / Q000187:drug effects; D020836:Protein Structure, Quaternary; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology; D047309:Flavones
chemical_list: D000251:Adenosine Triphosphatases; D001205:Ascorbic Acid; D003474:Curcumin; D056827:Endosomal Sorting Complexes Required for Transport; D005419:Flavonoids; D049452:Green Fluorescent Proteins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D024502:alpha-Tocopherol; C107528:VPS4 protein, S cerevisiae; C491128:Vps36 protein, S cerevisiae; C097188:polyglutamine; C008548:morin; D047309:Flavones