Adaptive responses to alloxan-induced mild oxidative stress ameliorate certain tauopathy phenotypes

Yuji Yoshiike, Shunji Yamashita, Tatsuya Mizoroki, Sumihiro Maeda, Miyuki Murayama, Tetsuya Kimura, Naruhiko Sahara, Yoshiyuki Soeda, Akihiko Takashima

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Oxidative stress is considered to promote aging and age-related disorders such as tauopathy. Although recent reports suggest that oxidative stress under certain conditions possesses anti-aging properties, no such conditions have been reported to ameliorate protein-misfolding diseases. Here, we used neuronal and murine models that overexpress human tau to demonstrate that mild oxidative stress generated by alloxan suppresses several phenotypes of tauopathy. Alloxan treatment reduced HSP90 levels and promoted proteasomal degradation of tau, c-Jun N-amino terminal kinase, and histone deacetylase (HDAC) 6. Moreover, reduced soluble tau (phosphorylated tau) levels suppressed the formation of insoluble tau in tau transgenic mice, while reduced HDAC6 levels contributed to microtubule stability by increasing tubulin acetylation. Age-dependent decreases in HDAC2 and phospho-tau levels correlated with spatial memory enhancement in alloxan-injected tau mice. These results suggest that mild oxidative stress, through adaptive stress responses, operates counteractively against some of the tauopathy phenotypes.

Original languageEnglish
Pages (from-to)51-62
Number of pages12
JournalAging Cell
Volume11
Issue number1
DOIs
Publication statusPublished - 2012 Feb 1
Externally publishedYes

Keywords

  • Aging
  • Alzheimer's disease
  • Memory
  • Microtubule
  • Oxidative stress
  • Tau

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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    Yoshiike, Y., Yamashita, S., Mizoroki, T., Maeda, S., Murayama, M., Kimura, T., Sahara, N., Soeda, Y., & Takashima, A. (2012). Adaptive responses to alloxan-induced mild oxidative stress ameliorate certain tauopathy phenotypes. Aging Cell, 11(1), 51-62. https://doi.org/10.1111/j.1474-9726.2011.00756.x