curcumin promotes a-beta fibrillation and reduces neurotoxicity in transgenic drosophila姜黄素促进a -β-淀粉样蛋白纤维性颤动,减少转基因果蝇的神经毒性.pdf

Curcumin Promotes A-beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila 1¤ 1 1 2 ¨ 1 Ina Caesar , Maria Jonson , K. Peter R. Nilsson , Stefan Thor , Per Hammarstrom * ¨ ¨ ¨ ¨ 1 IFM-Department of Chemistry, Linkoping University, Linkoping, Sweden, 2 IKE-Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden Abstract The pathology of Alzheimer’s disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-b (Ab) 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 Ab amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate Ab 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 Ab deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to Ab deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of Ab1–42 in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant Ab1–42. O