Inhibitory effect of curcumin on the Al(III)-induced Aβ₄₂ aggregation and neurotoxicity in vitro
© 2012 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1822 |
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| Enthalten in: |
Biochimica et biophysica acta - 1822(2012), 8 vom: 06. Aug., Seite 1207-15 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jiang, Teng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.01.2013 Date Revised 10.12.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbadis.2012.04.015 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM217561470 |
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| 520 | |a © 2012 Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Amyloid beta-Peptides |2 NLM | |
| 650 | 7 | |a Benzothiazoles |2 NLM | |
| 650 | 7 | |a Peptide Fragments |2 NLM | |
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| 700 | 1 | |a Zhi, Xiu-Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yue-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Luan-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ping |e verfasserin |4 aut | |
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