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

• MURAKAMI Kazuma

  Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University

• MURATA Nakaba

  Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology Applied Biological Chemistry, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology

• NODA Yoshihiro

  Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology

• IRIE Kazuhiro

  Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University

• SHIRASAWA Takuji

  Department of Aging Control Medicine, Juntendo University Graduate School of Medicine

• SHIMIZU Takahiko

  Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology Applied Biological Chemistry, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine

抄録

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.

収録刊行物

• Ｂｉｏｓｃｉｅｎｃｅ，　Ｂｉｏｔｅｃｈｎｏｌｏｇｙ，　ａｎｄ　Ｂｉｏｃｈｅｍｉｓｔｒｙ

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

  公益社団法人 日本農芸化学会

キーワード

• Alzheimer's disease
• amyloid β
• superoxide dismutase (SOD)
• superoxide radical
• oxidative stress

詳細情報

• CRID: 1390001206477971200
• NII論文ID: 10030817824
• NII書誌ID: AA10824164
• DOI: 10.1271/bbb.110934
• COI: 1:STN:280:DC%2BC38jps1Giug%3D%3D
• ISSN: 13476947
• ISSN: 09168451
• NDL書誌ID: 023768114
• PubMed: 22790929
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023768114
• 本文言語コード: en
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