The abnormal misfolding and aggregation of amyloid-beta (A beta) peptides into beta-sheet enriched insoluble deposits initiates a cascade of events leading to pathological processes and culminating in cognitive decline in Alzheimer's disease (AD). In particular, soluble oligomeric/prefibrillar A beta have been shown to be potent neurotoxins. The naturally occurring polyphenol curcumin has been shown to exert a neuroprotective effect against age-related neurodegenerative diseases such as AD. However, its protective mechanism remains unclear. In this study, we investigated the effects of curcumin on the aggregation of A beta 40 as well as A beta 40 aggregate induced neurotoxicity. Our results show that the curcumin does not inhibit A beta fibril formation, but rather enriches the population of "off-pathway" soluble oligomers and prefibrillar aggregates that were nontoxic. Curcumin also exerted a nonspecific neuroprotective effect, reducing toxicities induced by a range of A beta conformers, including monomeric, oligomeric, prefibrillar, and fibrillar A beta. The neuroprotective effect is possibly membrane-mediated, as curcumin reduced the extent of cell membrane permeabilization induced by A beta aggregates. Taken together, our study shows that curcumin exerts its neuroprotective effect against A beta induced toxicity through at least two concerted pathways, modifying the A beta aggregation pathway toward the formation of nontoxic aggregates and ameliorating A beta-induced toxicity possibly through a nonspecific pathway.
机构:
Seoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South KoreaSeoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South Korea
Bhak, Ghibom
;
Choe, Young-Jun
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Seoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South KoreaSeoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South Korea
Choe, Young-Jun
;
Paik, Seung R.
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Seoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South KoreaSeoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South Korea
机构:
Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Univ Chicago, James Franck Inst, Chicago, IL 60637 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Chi, Eva Y.
;
Ege, Canay
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Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Univ Chicago, James Franck Inst, Chicago, IL 60637 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Ege, Canay
;
Winans, Amy
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Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Univ Chicago, James Franck Inst, Chicago, IL 60637 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Winans, Amy
;
Majewski, Jaroslaw
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Los Alamos Natl Lab, Manuel Lujan Jr Neutron Scattering Ctr, Los Alamos Neutron Sci Ctr, Los Alamos, NM 87545 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Majewski, Jaroslaw
;
Wu, Guohui
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Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Univ Chicago, James Franck Inst, Chicago, IL 60637 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Wu, Guohui
;
Kjaer, Kristian
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Max Planck Inst Colloids & Interfaces, Am Muhlenberg, Germany
Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, DenmarkUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Kjaer, Kristian
;
Lee, Ka Yee C.
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Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Univ Chicago, James Franck Inst, Chicago, IL 60637 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
机构:
Seoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South KoreaSeoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South Korea
Bhak, Ghibom
;
Choe, Young-Jun
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h-index: 0
机构:
Seoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South KoreaSeoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South Korea
Choe, Young-Jun
;
Paik, Seung R.
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h-index: 0
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Seoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South KoreaSeoul Natl Univ, Coll Engn, Sch Chem & Biol Engn, Seoul 151744, South Korea
机构:
Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Univ Chicago, James Franck Inst, Chicago, IL 60637 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Chi, Eva Y.
;
Ege, Canay
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Univ Chicago, James Franck Inst, Chicago, IL 60637 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Ege, Canay
;
Winans, Amy
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机构:
Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Univ Chicago, James Franck Inst, Chicago, IL 60637 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Winans, Amy
;
Majewski, Jaroslaw
论文数: 0引用数: 0
h-index: 0
机构:
Los Alamos Natl Lab, Manuel Lujan Jr Neutron Scattering Ctr, Los Alamos Neutron Sci Ctr, Los Alamos, NM 87545 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Majewski, Jaroslaw
;
Wu, Guohui
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Univ Chicago, James Franck Inst, Chicago, IL 60637 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Wu, Guohui
;
Kjaer, Kristian
论文数: 0引用数: 0
h-index: 0
机构:
Max Planck Inst Colloids & Interfaces, Am Muhlenberg, Germany
Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, DenmarkUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Kjaer, Kristian
;
Lee, Ka Yee C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA
Univ Chicago, James Franck Inst, Chicago, IL 60637 USAUniv Chicago, Dept Chem, Inst Biophys Dynam, Chicago, IL 60637 USA