Document Type

Article

Publication Date

12-13-2006

Department

Biological Sciences

School

Biological, Environmental, and Earth Sciences

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 EGb 761 is mediated primarily by modulating Aβ oligomeric species, and (3) ginkgolide A has therapeutic potential for prevention and treatment of AD.

Publication Title

Journal of Neuroscience

Volume

26

Issue

50

First Page

13102

Last Page

13113

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