Curcumin Promotes A-beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila
2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 2Article in journal (Refereed) Published
The pathology of Alzheimers disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-beta (A beta) 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 A beta amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate A beta 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 A beta deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to A beta deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of A beta(1-42) in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant A beta(1-42). Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of A beta, resulting in a reduced neurotoxicity in Drosophila.
Place, publisher, year, edition, pages
Public Library of Science , 2012. Vol. 7, no 2
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-73502DOI: 10.1371/journal.pone.0031424ISI: 000302733900047OAI: oai:DiVA.org:liu-73502DiVA: diva2:473237
funding agencies|Knut and Alice Wallenberg foundation||Swedish Foundation for Strategic Research||Hjarnfonden||Swedish Research Council||Gustaf V. foundation||European Union||2012-01-052012-01-052014-04-08