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Title: Possible involvement of iron-induced oxidative insults in neurodegeneration.
Authors: Asano, Takeshi
Koike, Masato
Sakata, Shin-ichi
Takeda, Yukiko  kyouindb  KAKEN_id
Nakagawa, Tomoko
Hatano, Taku
Ohashi, Satoshi
Funayama, Manabu
Yoshimi, Kenji
Asanuma, Masato
Toyokuni, Shinya
Mochizuki, Hideki
Uchiyama, Yasuo
Hattori, Nobutaka
Iwai, Kazuhiro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-5620-5951 (unconfirmed)
Author's alias: 岩井, 一宏
Keywords: Iron
Iron regulatory protein
Oxidative stress
Mitochondria
Parkin
Parkinson’s disease
Issue Date: 19-Feb-2015
Publisher: Elsevier Ireland Ltd.
Journal title: Neuroscience letters
Volume: 588
Start page: 29
End page: 35
Abstract: 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.
Rights: © 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'.
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。This is not the published version. Please cite only the published version.
URI: http://hdl.handle.net/2433/201603
DOI(Published Version): 10.1016/j.neulet.2014.12.052
PubMed ID: 25549542
Appears in Collections:Journal Articles

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