Possible involvement of iron-induced oxidative insults in neurodegeneration

Takeshi Asano, Masato Koike, Shin ichi Sakata, Yukiko Takeda, Tomoko Nakagawa, Taku Hatano, Satoshi Ohashi, Manabu Funayama, Kenji Yoshimi, Masato Asanuma, Shinya Toyokuni, Hideki Mochizuki, Yasuo Uchiyama, Nobutaka Hattori, Kazuhiro Iwai

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)29-35
Number of pages7
JournalNeuroscience Letters
Volume588
Issue number1
DOIs
Publication statusPublished - Feb 9 2015

    Fingerprint

Keywords

  • Iron
  • Iron regulatory protein
  • Mitochondria
  • Oxidative stress
  • Parkin
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Asano, T., Koike, M., Sakata, S. I., Takeda, Y., Nakagawa, T., Hatano, T., Ohashi, S., Funayama, M., Yoshimi, K., Asanuma, M., Toyokuni, S., Mochizuki, H., Uchiyama, Y., Hattori, N., & Iwai, K. (2015). Possible involvement of iron-induced oxidative insults in neurodegeneration. Neuroscience Letters, 588(1), 29-35. https://doi.org/10.1016/j.neulet.2014.12.052