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Effect of Ischemic Neuronal Insults on Amyloid Precursor Protein Processing

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Abstract

The nature of the association between ischemic stroke and Alzheimer’s disease (AD) at the cellular and molecular level is still unknown. We evaluated the effect of ischemic neuronal insults on the regulation of amyloid precursor protein (APP) processing. We used an in vitro model of cerebral ischemia (oxygen-glucose deprivation) to evaluate the effect of ischemic neuronal insults on the amyloidogenic and non-amyloidogenic pathways using human neuroblastoma cell line and primary cultured cells of transgenic mice which expressed human APP (Tg2576). Ischemic neuronal insults increased the production of Aβ in Tg2576 primary culture cells compared to controls. A disintegrin and metalloprotease 10 (ADAM 10) was markedly increased in early stage of ischemic insults, which was followed by decreased level of ADAM 10 expression in later stage. The protein and mRNA expression of β-site cleavage enzyme (BACE) and BACE activity was not significantly different between the group of ischemic insults and control. By contrast, the activity of γ-secretase was significantly increased after 4 h of ischemic insults, as compared to controls. The present study showed that the ischemic neuronal insults increased the production of Aβ by influencing APP metabolism, which may link the role of ischemic insults to the pathogenesis of AD.

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Authors and Affiliations

  1. Department of Neurology, Ajou University School of Medicine, Woncheon-dong San 5, Youngtong-Ku, Suwon, Gyungki-do, 442-749, South Korea

    Phil Hyu Lee & Kyoon Huh

  2. Department of Biochemistry, Seoul National University School of Medicine, Seoul, Korea

    Eun Mi Hwang, Hyun Seok Hong, Jung Hyun Boo & Inhee Mook-Jung

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  1. Phil Hyu Lee
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  2. Eun Mi Hwang
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  3. Hyun Seok Hong
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  5. Inhee Mook-Jung
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  6. Kyoon Huh
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Correspondence to Kyoon Huh.

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Lee, P.H., Hwang, E.M., Hong, H.S. et al. Effect of Ischemic Neuronal Insults on Amyloid Precursor Protein Processing. Neurochem Res 31, 821–827 (2006). https://doi.org/10.1007/s11064-006-9086-y

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  • DOI: https://doi.org/10.1007/s11064-006-9086-y

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