Inhibitory effect of curcumin on the Al(III)-induced Aβ42 aggregation and neurotoxicity in vitro

Abstract

The pathogenesis of Alzheimer's disease (AD) involves a key event which changes the morphology of amyloid-β 42 (Aβ42) peptide from its soluble monomeric form into the fibrillated aggregates in the brain. Aluminum ion, Al(III), is known to act as a pathological chaperone of the Aβ42 in this process; curcumin, a natural phenolic compound, is considered capable of binding Al(III) and Aβ42; nevertheless, little is known about the combined action of curcumin and Al(III) on the Aβ42 fibrillation and neurotoxicity. Here, combinations of circular dichroism spectroscopy, thioflavin T fluorescence, atomic force microscopy, Bradford and MTT assays, it is demonstrated that although Al(III) can promote the Aβ42 fibrillation dose-dependently, leading to the high neurotoxicity to PC12 cells, curcumin can inhibit the events. Besides, we found that curcumin is able not only to inhibit the formation of Al(III)-induced Aβ42 fibrillation, but also to form the Al(III)–curcumin complexes which in turn can remold the preformed, mature, ordered Aβ42 fibrils into the low toxic amorphous aggregates. These findings suggest that curcumin could block the binding of Al(III) with Aβ42 and form the Al(III)–curcumin complexes, so as to inhibit the Al(III)-induced Aβ42 fibrillation and neurotoxicity. The Al(III)–curcumin complexes are worth potentially developing as a therapy agent against the neurodegenerative disorders in the future.