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ACS Chem Neurosci. 2016 Jan 20;7(1):56-68. doi: 10.1021/acschemneuro.5b00214. Epub 2015 Nov 17.

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

Author information

1
Department of Chemical and Biological Engineering and the Center for Biomedical Engineering, and ‡Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, University of New Mexico , Albuquerque, New Mexico 87131, United States.

Abstract

The abnormal misfolding and aggregation of amyloid-β (Aβ) peptides into β-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 Aβ 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 Aβ40 as well as Aβ40 aggregate induced neurotoxicity. Our results show that the curcumin does not inhibit Aβ 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 Aβ conformers, including monomeric, oligomeric, prefibrillar, and fibrillar Aβ. The neuroprotective effect is possibly membrane-mediated, as curcumin reduced the extent of cell membrane permeabilization induced by Aβ aggregates. Taken together, our study shows that curcumin exerts its neuroprotective effect against Aβ induced toxicity through at least two concerted pathways, modifying the Aβ aggregation pathway toward the formation of nontoxic aggregates and ameliorating Aβ-induced toxicity possibly through a nonspecific pathway.

KEYWORDS:

Alzheimer’s disease; Aβ aggregation; amyloid-β peptide (Aβ); curcumin; neuroprotection; toxicity

PMID:
26529184
DOI:
10.1021/acschemneuro.5b00214
[Indexed for MEDLINE]

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