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j.neulet.2014.12.052.pdf | 1.7 MB | Adobe PDF | 見る/開く |
タイトル: | Possible involvement of iron-induced oxidative insults in neurodegeneration. |
著者: | Asano, Takeshi Koike, Masato Sakata, Shin-ichi Takeda, Yukiko Nakagawa, Tomoko Hatano, Taku Ohashi, Satoshi Funayama, Manabu Yoshimi, Kenji Asanuma, Masato Toyokuni, Shinya Mochizuki, Hideki Uchiyama, Yasuo Hattori, Nobutaka Iwai, Kazuhiro https://orcid.org/0000-0001-5620-5951 (unconfirmed) |
著者名の別形: | 岩井, 一宏 |
キーワード: | Iron Iron regulatory protein Oxidative stress Mitochondria Parkin Parkinson’s disease |
発行日: | 19-Feb-2015 |
出版者: | Elsevier Ireland Ltd. |
誌名: | Neuroscience letters |
巻: | 588 |
開始ページ: | 29 |
終了ページ: | 35 |
抄録: | Involvement of iron in the development of neurodegenerative disorders has long been suggested, and iron that cannot be stored properly is suggested to induce iron toxicity. To enhance iron uptake and suppress iron storage in neurons, we generated transgenic (Tg) mice expressing iron regulatory protein 2 (IRP2), a major regulator of iron metabolism, in a neuron-specific manner. Although very subtle, IRP2 was expressed in all regions of brain examined. In the Tg mice, mitochondrial oxidative insults were observed including generation of 4-hydroxynonenal modified proteins, which appeared to be removed by a mitochondrial quality control protein Parkin. Inter-crossing of the Tg mice to Parkin knockout mice perturbed the integrity of neurons in the substantia nigra and provoked motor symptoms. These results suggest that a subtle, but chronic increase in IRP2 induces mitochondrial oxidative insults and accelerates neurodegeneration in a mouse model of Parkinson's disease. Thus, the IRP2 Tg may be a useful tool to probe the roles of iron-induced mitochondrial damages in neurodegeraration research. |
著作権等: | © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ The full-text file will be made open to the public on 19 February 2016 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/201603 |
DOI(出版社版): | 10.1016/j.neulet.2014.12.052 |
PubMed ID: | 25549542 |
出現コレクション: | 学術雑誌掲載論文等 |
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