Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Manabe, Tatsuoa; 1 | Matsumura, Akihiroa; 1 | Yokokawa, Kazukia | Saito, Taroa | Fujikura, Maia | Iwahara, Naotoshia | Matsushita, Takashia | Suzuki, Syuuichiroua | Hisahara, Shina | Kawamata, Juna | Suzuki, Hiromia | Emoto, Miho C.b | Fujii, Hirotada G.b | Shimohama, Shuna; *
Affiliations: [a] Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan | [b] Health Sciences University of Hokkaido, Sapporo, Japan
Correspondence: [*] Correspondence to: Dr. Shun Shimohama, Department of Neurology, School of Medicine, Sapporo Medical University, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan. Tel.: +81-11-611-2111; Fax: +81-11-622-7668; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
Abstract: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases responsible for progressive dementia. Deposition of amyloid-β (Aβ) in the brain is the most important pathophysiological hallmark of AD. In addition, recent evidence indicates that reactive oxygen species (ROS) derived from mitochondria contribute to progression of AD pathology. We thus hypothesized that Aβ accumulates and oxidative stress increases in the brain mitochondria of a transgenic mouse model of AD (APdE9). We measured the quantity of Aβ and the activity of the antioxidant enzyme superoxide dismutase (SOD) in brain mitochondrial fractions prepared from APdE9 and wild-type (WT) mice aged 6, 9, 15, and 18 months. We also quantified the age-related changes in redox status in the mitochondrial fractions obtained from both APdE9 and WT mouse brains by electron paramagnetic resonance (EPR) spectrometry using a paramagnetic nitroxide “Mito-Tempo” [(2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride monohydrate] as a mitochondria-targeted redox-sensitive probe. In APdE9 mice, Aβ accumulated in brain mitochondria earlier than in the non-mitochondrial fraction of the brain. Furthermore, increased oxidative stress was demonstrated in brain mitochondria of APdE9 mice by in vitro SOD assay as well as EPR spectroscopy. EPR combined with a mitochondria-targeted redox-sensitive nitroxide probe is a potentially powerful tool to elucidate the etiology of AD and facilitate the development of new therapeutic strategies for AD.
Keywords: Alzheimer’s disease, amyloid-β, electron paramagnetic resonance, mitochondria, reactive oxygen special, redox status, oxidative stress
DOI: 10.3233/JAD-180985
Journal: Journal of Alzheimer's Disease, vol. 67, no. 3, pp. 1079-1087, 2019
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
[email protected]
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office [email protected]
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
如果您在出版方面需要帮助或有任何建, 件至: [email protected]