Pioglitazone prevents tau oligomerization

Tadanori Hamano, Norimichi Shirafuji, Chiemi Makino, Shu Hui Yen, Nicholas M. Kanaan, Asako Ueno, Jinya Suzuki, Masamichi Ikawa, Akiko Matsunaga, Osamu Yamamura, Masaru Kuriyama, Yasunari Nakamoto

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Tau aggregation and amyloid β protein (Aβ) deposition are the main causes of Alzheimer's disease (AD). Peroxisome proliferator-activated receptor γ (PPARγ) activation modulates Aβ production. To test whether the PPARγ agonist pioglitazone (PIO) is also effective in preventing tau aggregation in AD, we used a cellular model in which wild-type tau protein (4R0N) is overexpressed (M1C cells) (Hamano et al., 2012) as well as primary neuronal cultures. PIO reduced both phosphorylated and total tau levels, and inactivated glycogen synthase kinase 3β, a major tau kinase, associated with activation of Akt. In addition, PIO decreased cleaved caspase3 and C-terminal truncated tau species by caspase, which is expected to decrease tau aggregation. A fractionation study showed that PIO reduced high molecular-weight (120 kDa), oligomeric tau species in Tris Insoluble, sarkosyl-soluble fractions. Tau decrease was reversed by adding GW9662, a PPARγ antagonist. Together, our current results support the idea that PPARγ agonists may be useful therapeutic agents for AD.

Original languageEnglish (US)
Pages (from-to)1035-1042
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume478
Issue number3
DOIs
StatePublished - 2016

Keywords

  • Caspase
  • GSK3β
  • Phosphorylation
  • Pioglitazone
  • PPARγ
  • Tau
  • Tau oligomer

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Hamano, T., Shirafuji, N., Makino, C., Yen, S. H., Kanaan, N. M., Ueno, A., Suzuki, J., Ikawa, M., Matsunaga, A., Yamamura, O., Kuriyama, M., & Nakamoto, Y. (2016). Pioglitazone prevents tau oligomerization. Biochemical and Biophysical Research Communications, 478(3), 1035-1042. https://doi.org/10.1016/j.bbrc.2016.08.016