Amyloid-β-induced pathological behaviors are suppressed by Ginkgo biloba extract EGB 761 and ginkgolides in transgenic Caenorhabditis elegans

Yanjue Wu, Zhixin Wu, Peter Butko, Yves Christen, Mary P. Lambert, William L. Klein, Christopher D. Link, Yuan Luo*

*Corresponding author for this work

Research output: Contribution to journalArticle

244 Scopus citations

Abstract

Amyloid-β(Aβ) toxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration seen in Alzheimer's disease (AD). We previously demonstrated that the standardized Ginkgo biloba extract EGb 761, commonly used to enhance memory and by AD patients for dementia, inhibits Aβ-induced apoptosis in neuroblastoma cells. In this study, we use EGb 761 and its single constituents to associate Aβ species with Aβ-induced pathological behaviors in a model organism, Caenorhabditis elegans. We report that EGb 761 and one of its components, ginkgolide A, alleviates Aβ-induced pathological behaviors, including paralysis, and reduces chemotaxis behavior and 5-HT hypersensitivity in a transgenic C. elegans. We also show that EGb 761 inhibits Aβ oligomerization and Aβ deposits in the worms. Moreover, reducing oxidative stress is not the mechanism by which EGb 761 and ginkgolide A suppress Aβ-induced paralysis because the antioxidant L-ascorbic acid reduced intracellular levels of hydrogen peroxide to the same extent as EGb 761, but was not nearly as effective in suppressing paralysis in the transgenic C. elegans. These findings suggest that (1) EGb 761 suppresses Aβ-related pathological behaviors, (2) the protection against Aβ toxicity by EGb761 is mediated primarily by modulating Aβ oligomeric species, and (3) ginkgolide A has therapeutic potential for prevention and treatment of AD.

Original languageEnglish (US)
Pages (from-to)13102-13113
Number of pages12
JournalJournal of Neuroscience
Volume26
Issue number50
DOIs
StatePublished - Dec 13 2006

Keywords

  • Alzheimer's disease
  • Aβ peptide
  • Behavior
  • Mutant
  • Phenotype
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)

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