title: Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.
abstract: The pathology of Alzheimer's disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-β (Aβ) peptide and intraneuronal accumulation of tangles comprised of hyperphosphorylated Tau protein. For several years, the natural compound curcumin has been proposed to be a candidate for enhanced clearance of toxic Aβ amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate Aβ toxicity in transgenic Drosophila. The longevity as well as the locomotor activity of five different AD model genotypes, measured relative to a control line, showed up to 75% improved lifespan and activity for curcumin fed flies. In contrast to the majority of studies of curcumin effects on amyloid we did not observe any decrease in the amount of Aβ deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to Aβ deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of Aβ(1-42) in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant Aβ(1-42). Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of Aβ, resulting in a reduced neurotoxicity in Drosophila.
authors.affiliation: IFM-Department of Chemistry, Linköping University, Linköping, Sweden.
authors.forename: Ina
authors.initials: I
authors.lastname: Caesar
authors.forename: Maria
authors.initials: M
authors.lastname: Jonson
authors.forename: K Peter R
authors.initials: KP
authors.lastname: Nilsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Thor
authors.forename: Per
authors.initials: P
authors.lastname: Hammarström
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004330:Drosophila; D005838:Genotype; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D058105:Polymerization / Q000187:drug effects*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D016229:Amyloid beta-Peptides; D003474:Curcumin