Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1822, Issue 8, Pages 1207-1215Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2012.04.015
Keywords
Alzheimer's disease; Protein conformation; Aggregate morphology; Fibrillation inhibitor
Funding
- Natural Science Foundation of China [10475017, 20673022, 21074025]
- Action Plan of Science and Technology Innovation, Science and Technology Commission of Shanghai Municipality [11DZ1971802]
- Research Innovation Project, Education Commission of Shanghai Municipality [12ZZ009]
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The pathogenesis of Alzheimer's disease (AD) involves a key event which changes the morphology of amyloid-beta 42 (A beta(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 A beta(42) in this process; curcumin, a natural phenolic compound, is considered capable of binding Al(III) and A beta(42); nevertheless, little is known about the combined action of curcumin and Al(III) on the A beta(42) 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 A beta(42) 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 A beta(42) fibrillation, but also to form the Al(III)-curcumin complexes which in turn can remold the preformed, mature, ordered A beta(42) fibrils into the low toxic amorphous aggregates. These findings suggest that curcumin could block the binding of Al(III) with A beta(42) and form the Al(III)-curcumin complexes, so as to inhibit the Al(III)-induced A beta(42) fibrillation and neurotoxicity. The Al(III)-curcumin complexes are worth potentially developing as a therapy agent against the neurodegenerative disorders in the future. (C) 2012 Elsevier B.V. All rights reserved,
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