Affiliations: Laboratory of Cellular and Molecular Neuroscience, Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA
Correspondence:
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Corresponding author: Yuan Luo, Department of Biological Sciences, University of Southern Mississippi, 2609 W 4th Street, Hattiesburg, MS 39406-5018, USA. Tel.: +1 601 266 5417; Fax: +1 601 266 5797; E-mail: [email protected].
Abstract: The role of amyloid β-peptide (Aβ) in the free-radical oxidative-stress model of neurotoxicity in Alzheimer's disease (AD) has received much attention recently. In this study, we have employed both in vitro and in vivo models displaying endogenous Aβproduction to study the effects of Aβ on intracellular free radical levels. We employed a neuroblastoma cell line stably expressing an AD-associated double mutation, which exhibits both increased secretion and intracellular accumulation of Aβ when stimulated, as well as transgenic Caenorhabditis elegans constitutively expressing human Aβ. A rise in levels of hydrogen peroxide (H2O2) was observed in both in vitro and in vivo AD-associated transgenic models expressing the Aβ peptide compared with the wild type controls. Treatment of the cells or C. elegans with Ginkgo biloba extract EGb 761 significantly attenuated the basal as well as the induced levels of H2O2-related reactive oxygen species (ROS). Among individual EGb 761 components tested, kaempferol and quercetin provided maximum attenuation in both models. Furthermore, an age-dependent increase in H2O2-related ROS was observed in wild type C. elegans, which is accelerated in the AD-associated C. elegans mutant. These results support the hypothesis of the involvement of Aβ and ROS in association with AD.
