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PLoS By Category | Recent PLoS Articles
Biochemistry - Biophysics - Chemistry - Neurological Disorders - Neuroscience

Curcumin Promotes A-beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila
Published: Monday, February 13, 2012
Author: Ina Caesar et al.

by Ina Caesar, Maria Jonson, K. Peter R. Nilsson, Stefan Thor, Per Hammarström

The pathology of Alzheimer's disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-ß (Aß) 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 Aß amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate Aß 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 Aß deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to Aß deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of Aß1–42 in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant Aß1–42. Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of Aß, resulting in a reduced neurotoxicity in Drosophila.
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