title: 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 (Aβ)₄₂ 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.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Zhi
authors.forename: Yue-Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Luan-Feng
authors.initials: LF
authors.lastname: Pan
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
mesh_terms: D000535:Aluminum / Q000737:chemistry* / Q000633:toxicity; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles; D002942:Circular Dichroism; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology*; D018625:Microscopy, Atomic Force; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D013844:Thiazoles / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C009462:thioflavin T; D000535:Aluminum; D003474:Curcumin