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
Search this article
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.
Journal
-
- Bioscience, Biotechnology, and Biochemistry
-
Bioscience, Biotechnology, and Biochemistry 76 (6), 1098-1103, 2012
Japan Society for Bioscience, Biotechnology, and Agrochemistry
- Tweet
Keywords
Details 詳細情報について
-
- CRID
- 1390001206477971200
-
- NII Article ID
- 10030817824
-
- NII Book ID
- AA10824164
-
- COI
- 1:STN:280:DC%2BC38jps1Giug%3D%3D
-
- ISSN
- 13476947
- 09168451
-
- NDL BIB ID
- 023768114
-
- PubMed
- 22790929
-
- Text Lang
- en
-
- Data Source
-
- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
-
- Abstract License Flag
- Disallowed