Stimulation of the Amyloidogenic Pathway by Cytoplasmic Superoxide Radicals in an Alzheimer's Disease Mouse Model

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Author(s)

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 (<i>hAPP</i>/<i>Sod1</i><sup>−/−</sup>). 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 <i>Sod1</i> deficiency enhanced β-cleavage of hAPP, suggesting that it increased Aβ production in <i>hAPP</i>/<i>Sod1</i><sup>−/−</sup> mice. In contrast, Aβ degradation did not decrease in <i>hAPP</i>/<i>Sod1</i><sup>−/−</sup> as compared with <i>hAPP</i>/<i>Sod1</i><sup>+/+</sup> mice. Furthermore, we successfully detected <i>in situ</i> superoxide radicals associated with increased protein carbonylation in <i>hAPP</i>/<i>Sod1</i><sup>−/−</sup>. These results suggest that cytoplasmic oxidative stress is involved in Aβ production as well as aggregation during AD progression.

Journal

  • Bioscience, Biotechnology, and Biochemistry

    Bioscience, Biotechnology, and Biochemistry 76(6), 1098-1103, 2012-06-23

    Japan Society for Bioscience, Biotechnology, and Agrochemistry

References:  48

Codes

  • NII Article ID (NAID)
    10030817824
  • NII NACSIS-CAT ID (NCID)
    AA10824164
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    09168451
  • NDL Article ID
    023768114
  • NDL Call No.
    Z53-G223
  • Data Source
    CJP  NDL  J-STAGE 
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