Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila.

Authors: Caesar I; Jonson M; Nilsson KP; Thor S; Hammarström P

Abstract: The pathology of Alzheimer's disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-beta (Abeta) 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 Abeta amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate Abeta 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 Abeta deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to Abeta deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of Abeta(1-42) in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant Abeta(1-42). Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of Abeta, resulting in a reduced neurotoxicity in Drosophila.

Keywords: Alzheimer Disease/drug therapy; Amyloid beta-Peptides/*drug effects/metabolism; Animals; Animals, Genetically Modified; Curcumin/administration & dosage/*pharmacology/therapeutic use; Drosophila; Genotype; Neurotoxicity Syndromes/*prevention & control; Polymerization/*drug effects; Survival Rate; Treatment Outcome
Journal: PloS one
Volume: 7
Issue: 2
Pages: e31424
Date: Feb. 22, 2012
PMID: 22348084
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Citation:

Caesar I, Jonson M, Nilsson KP, Thor S, Hammarström P (2012) Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila. PloS one 7: e31424.


Study Lifespan Factors:
  • Curcumin


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