Pioglitazone prevents tau oligomerization

Journal Article · Fri Sep 23 04:00:00 EDT 2016 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2016.08.016· OSTI ID:22696597

Hamano, Tadanori ^[1]; Shirafuji, Norimichi; Makino, Chiemi ^[1]; Yen, Shu-Hui ^[2]; Kanaan, Nicholas M. ^[3]; Ueno, Asako ^[1]; Suzuki, Jinya ^[4]; Ikawa, Masamichi; Matsunaga, Akiko; Yamamura, Osamu ^[1]; Kuriyama, Masaru ^[5]; Nakamoto, Yasunari ^[1]

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1. Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)
2. Department of Neuroscience, Mayo Clinic College Florida, Jacksonville, FL (United States)
3. Department of Translational Science and Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI (United States)
4. Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)
5. Brain Attack Ota Memorial Hospital, Fukuyama (Japan)

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. - Highlights: • PPARγ agonist pioglitazone decreased tau oligomerization. • The mechanism lies on the reduction of phosphorylated tau and caspase cleaved tau. • Pioglitazone inactivated GSK3β and caspase3. • Tau decrease was reversed by the PPAR γ antagonist GW9662.

• OSTI ID: 22696597
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 478; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AGGLOMERATION
CURRENTS
DEPOSITION
DISEASES
DRUGS
FRACTIONATION
GLYCOGEN
MOLECULAR WEIGHT
PHOSPHORYLATION
PHOSPHOTRANSFERASES
RECEPTORS
REDUCTION
SUPPORTS