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.

Chitosan Oligosaccharides Inhibit/Disaggregate Fibrils and Attenuate Amyloid β-Mediated Neurotoxicity

“…However, as shown in Figure 1B, the CD spectra of 50 μM Aβ42 coincubated with 2.5 or 5.0 mg/mL COS for 48 h suggested a largely disordered structure. The conformational conversion of 50 μM Aβ42 from physiological unfolded random coil to β-sheet structure was partly suppressed by 2.5 mg/mL COS addition, manifested by decreased negative band at ~216 nm compared to Aβ42 alone; while with addition of 5.0 mg/mL COS, the spectrum appeared a broader negative band at ~200 nm suggesting the secondary structure of Aβ is mainly random coil [15]. These results suggest that COS could prevent Aβ from converting into β-sheet structure in a dose-dependent manner, where COS at a concentration of 5.0 mg/mL was more effective than that of 2.5 mg/mL in inhibiting β-structure formation.…”

“…Cortical neuronal cultures were carried out as described previously [15]. Briefly, embryonic day 17 Sprague Dawley rat cortices were dissociated and suspended in fresh neurobasal medium plus 2% B27 supplements, then plated onto poly- d -lysine-coated 96-well culture plates at a density of 5 × 10 4 cells per well and maintained at 37 °C in CO 2 incubator.…”

Gelsolin bound β-amyloid peptides (1–40/1–42) : Electrochemical evaluation of levels of soluble peptide associated with Alzheimer's disease

“…The concept of the primary role of Aβ in AD neuropathology has been reinforced by the well-established Aβ accumulation in the brains of AD sufferers (Borchelt et al, 1996). The peptide accumulation is a progressive course, in which a key event of changes in the morphology of Aβ are involved, from its soluble monomeric form into oligomers and fibrillated aggregates in the brain (Jiang et al, 2012), thus reduces the amount of soluble Aβ 1-40 and Aβ 1-42 monomers in brain. It should be highlighted that this work innovatively realized the assessment of Aβ levels both in CSF and three brain tissues sampled from AD rats, which was more comprehensive and reliable to understand the pathogenesis of this neurodegenerative disease than those that focused only on CSF determination, as we mentioned above that the peptide aggregation in AD occurs not only in CSF but also in brain tissues.…”

Effects of curcumin on hippocampal expression of NgR and axonal regeneration in Aβ-induced cognitive disorder rats

“…Based on its chemical characteristics and results of clinical applications, it appears that curcumin is an effective therapeutic drug with promising prospects for treating AD (Cole et al, 2004;Wang et al, 2012;Jiang et al, 2012). The mechanism of action of curcumin and its target are very complex, and need further investigation.…”