Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42

Ruitian Liu, Hedieh Barkhordarian, Sharareh Emadi, Beum Park Chan, Michael Sierks

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

A key event in Alzheimer's disease (AD) pathogenesis is the conversion of the peptide beta-amyloid (Aβ) from its soluble monomeric form into various aggregated morphologies in the brain. Preventing aggregation of Aβ is being actively pursued as a primary therapeutic strategy for treating AD. Trehalose, a simple disaccharide, has been shown to be effective in preventing the deactivation of numerous proteins and in protecting cells against stress. Here, we show that trehalose is also effective in inhibiting aggregation of Aβ and reducing its cytotoxicity, although it shows differential effects toward Aβ40 and Aβ42. When co-incubated with Aβ40, trehalose inhibits formation of both fibrillar and oligomeric morphologies as determined by fluorescence staining and atomic force microscopy (AFM). However, when co-incubated with Aβ42, trehalose inhibits formation only of the fibrillar morphology, with significant oligomeric formation still present. When aggregated mixtures were incubated with SH-SY5Y cells, trehalose was shown to reduce the toxicity of Aβ40 mixtures, but not Aβ42. These results provide additional evidence that aggregation of Aβ into soluble oligomeric forms is a pathological step in AD and that Aβ42 in particular is more susceptible to forming these toxic oligomers than Aβ40. These results also suggest that the use of trehalose, a highly soluble, low-priced sugar, as part of a potential therapeutic cocktail to control Aβ peptide aggregation and toxicity warrants further study.

Original languageEnglish (US)
Pages (from-to)74-81
Number of pages8
JournalNeurobiology of Disease
Volume20
Issue number1
DOIs
StatePublished - Oct 2005

Fingerprint

Trehalose
Amyloid
Alzheimer Disease
Atomic Force Microscopy
Disaccharides
Poisons
Amyloid beta-Peptides
Fluorescence
Staining and Labeling
Peptides
Brain
Therapeutics
Proteins

Keywords

  • Aggregation
  • Alzheimer's disease
  • Atomic force microscope
  • Beta-amyloid
  • Cytotoxicity
  • Oligomers
  • Trehalose

ASJC Scopus subject areas

  • Neurology

Cite this

Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42. / Liu, Ruitian; Barkhordarian, Hedieh; Emadi, Sharareh; Chan, Beum Park; Sierks, Michael.

In: Neurobiology of Disease, Vol. 20, No. 1, 10.2005, p. 74-81.

Research output: Contribution to journalArticle

Liu, Ruitian ; Barkhordarian, Hedieh ; Emadi, Sharareh ; Chan, Beum Park ; Sierks, Michael. / Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42. In: Neurobiology of Disease. 2005 ; Vol. 20, No. 1. pp. 74-81.
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