Bioscience, Biotechnology, and Biochemistry
Biochemistry & Molecular Biology Regular Papers
Stimulation of the Amyloidogenic Pathway by Cytoplasmic Superoxide Radicals in an Alzheimer's Disease Mouse Model
Kazuma MURAKAMINakaba MURATAYoshihiro NODAKazuhiro IRIETakuji SHIRASAWATakahiko SHIMIZU
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Volume 76 (2012) Issue 6 Pages 1098-1103

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Abstract

Oxidative stress is involved in the pathogenesis of neurodegeneration. Amyloid β (Aβ) oligomer as an intermediate of aggregates causes memory loss in Alzheimer's disease (AD). We have suggested that oxidative stress plays an important role in Aβ oligomerization and cognitive impairment using a human amyloid precursor protein (hAPP) transgenic AD mice lacking cytoplasmic superoxide dismutase (hAPP/Sod1−/−). Recently, clinical trials revealed inhibitors of Aβ production from hAPP as promising therapeutics, but the relationship between oxidative stress and Aβ metabolism remains unclear. Here we found that Sod1 deficiency enhanced β-cleavage of hAPP, suggesting that it increased Aβ production in hAPP/Sod1−/− mice. In contrast, Aβ degradation did not decrease in hAPP/Sod1−/− as compared with hAPP/Sod1+/+ mice. Furthermore, we successfully detected in situ superoxide radicals associated with increased protein carbonylation in hAPP/Sod1−/−. These results suggest that cytoplasmic oxidative stress is involved in Aβ production as well as aggregation during AD progression.

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© 2012 by Japan Society for Bioscience, Biotechnology, and Agrochemistry
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