Membrane-mediated neuroprotection by curcumin from amyloid-β-peptide- induced toxicity

Amyloid-β peptide (Aβ)-membrane interactions have been implicated in the formation of toxic oligomers that permeabilize membranes, allowing an influx of calcium ions and triggering cell death in the pathogenesis of Alzheimer's disease (AD). Curcumin, a small dietary polyphenolic molecule, has been shown to reduce Aβ-induced toxicity and AD pathology. We investigate here the effect of curcumin on Aβ40-induced toxicity in cultured human neuroblastoma SH-SY5Y cells and test a novel neuroprotection mechanism in which curcumin reduces Aβ-membrane interactions and attenuates Aβ-induced membrane disruptions. Predominantly monomeric Aβ40 exerts toxicity toward SH-SY5Y cells and has been shown to insert spontaneously into anionic lipid monolayers at the air/water interface, resulting in the misfolding and assembly of Aβ into β-sheet-enriched oligomers. Concomitantly, membrane morphology and lipid packing are disrupted. Curcumin dose-dependently ameliorates Aβ-induced neurotoxicity and reduces either the rate or extent of Aβ insertion into anionic lipid monolayers. Moreover, curcumin reduces Aβ-induced dye leakage from lipid-bilayer-covered, dye-loaded, porous silica microspheres. Because curcumin neither affects the inherent surface activity of Aβ nor modifies the membrane properties, it reduces Aβ insertion by directly attenuating Aβ-membrane interactions and reducing Aβ-induced membrane disruption. Although the exact molecular mechanism of curcumin's membrane protective effect remains unclear, this effect could in part contribute to curcumin's neuroprotective effect with respect to Aβ-induced toxicity. Our work reveals a novel molecular mechanism by which curcumin reduces Aβ-related pathology and toxicity and suggests a therapeutic strategy for preventing or treating AD by targeting the inhibition of Aβ-induced membrane disruption. © 2013 American Chemical Society.

Full Text

Duke Authors

Cited Authors

  • Thapa, A; Vernon, BC; Peña, KDL; Soliz, G; Moreno, HA; López, GP; Chi, EY

Published Date

  • 2013

Published In

Volume / Issue

  • 29 / 37

Start / End Page

  • 11713 - 11723

PubMed ID

  • 24004419

International Standard Serial Number (ISSN)

  • 0743-7463

Digital Object Identifier (DOI)

  • 10.1021/la4020459

Citation Source

  • SciVal