Curcumin Attenuates Arnyloid-β Aggregate Toxicity and Modulates Amyloid-β Aggregation Pathway

被引:145
作者
Thapa, Arjun [1 ,2 ]
Jett, Stephen D. [3 ]
Chi, Eva Y. [1 ,2 ]
机构
[1] Univ New Mexico, Hlth Sci Ctr, Dept Chem & Biol Engn, Albuquerque, NM 87131 USA
[2] Univ New Mexico, Hlth Sci Ctr, Ctr Biomed Engn, Albuquerque, NM 87131 USA
[3] Univ New Mexico, Hlth Sci Ctr, Dept Cell Biol & Physiol, Albuquerque, NM 87131 USA
基金
美国国家科学基金会;
关键词
Alzheimer's disease; amyloid-beta peptide (A beta); A beta aggregation; toxicity; curcumin; neuroprotection; SMALL-MOLECULE INHIBITORS; A-BETA; ALZHEIMERS-DISEASE; POLYPHENOLIC COMPOUNDS; MEMBRANE DISRUPTION; PRECURSOR PROTEIN; FIBRIL FORMATION; IN-VITRO; OLIGOMERS; PEPTIDE;
D O I
10.1021/acschemneuro.5b00214
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:56 / 68
页数:13
相关论文
共 82 条
[1]   CURCUMINOIDS ENHANCE MEMORY IN AN AMYLOID-INFUSED RAT MODEL OF ALZHEIMER'S DISEASE [J].
Ahmed, T. ;
Enam, S. A. ;
Gilani, A. H. .
NEUROSCIENCE, 2010, 169 (03) :1296-1306
[2]   Curcuminoids Rescue Long-Term Potentiation Impaired by Amyloid Peptide in Rat Hippocampal Slices [J].
Ahmed, Touqeer ;
Gilani, Anwarul-Hassan ;
Hosseinmardi, Narges ;
Semnanian, Saeed ;
Enam, Syed Ather ;
Fathollahi, Yaghoub .
SYNAPSE, 2011, 65 (07) :572-582
[3]  
Baum L, 2004, J ALZHEIMERS DIS, V6, P367
[4]   Atomistic mechanism of polyphenol amyloid aggregation inhibitors: molecular dynamics study of Curcumin, Exifone, and Myricetin interaction with the segment of tau peptide oligomer [J].
Berhanu, Workalemahu M. ;
Masunov, Artem E. .
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2015, 33 (07) :1399-1411
[5]   Mechanism of amyloidogenesis: nucleation-dependent fibrillation versus double-concerted fibrillation [J].
Bhak, Ghibom ;
Choe, Young-Jun ;
Paik, Seung R. .
BMB REPORTS, 2009, 42 (09) :541-551
[6]   EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity [J].
Bieschke, Jan ;
Russ, Jenny ;
Friedrich, Ralf P. ;
Ehrnhoefer, Dagmar E. ;
Wobst, Heike ;
Neugebauer, Katja ;
Wanker, Erich E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (17) :7710-7715
[7]   Alzheimer's disease [J].
Scheltens, Philip ;
De Strooper, Bart ;
Kivipelto, Miia ;
Holstege, Henne ;
Chetelat, Gael ;
Teunissen, Charlotte E. ;
Cummings, Jeffrey ;
van der Flier, Wiesje M. .
LANCET, 2021, 397 (10284) :1577-1590
[8]   Curcumin Promotes A-beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila [J].
Caesar, Ina ;
Jonson, Maria ;
Nilsson, K. Peter R. ;
Thor, Stefan ;
Hammarstrom, Per .
PLOS ONE, 2012, 7 (02)
[9]   Lipid membrane templates the ordering and induces the fibrillogenesis of Alzheimer's disease amyloid-β peptide [J].
Chi, Eva Y. ;
Ege, Canay ;
Winans, Amy ;
Majewski, Jaroslaw ;
Wu, Guohui ;
Kjaer, Kristian ;
Lee, Ka Yee C. .
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2008, 72 (01) :1-24
[10]   Ganglioside GM1-mediated amyloid-beta fibrillogenesis and membrane disruption [J].
Chi, Eva Y. ;
Frey, Shelli L. ;
Lee, Ka Yee C. .
BIOCHEMISTRY, 2007, 46 (07) :1913-1924