Nobiletin restoring β-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer's disease model rats

Kentaro Matsuzaki, Tohru Yamakuni, Michio Hashimoto, Abdul Md Haque, Osamu Shido, Yoshihiro Mimaki, Yutaka Sashida, Yasushi Ohizumi

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive and memory deterioration. Production and accumulation of β-amyloid peptide (Aβ) is central to the pathogenesis of AD. Recent studies have demonstrated that PKA/CREB-dependent signaling pathway and long-term potentiation are inhibited by sublethal concentrations of Aβ1-42 in cultured hippocampus neurons. Here, we examined the effects of nobiletin on the Aβ-induced inhibition of CREB phosphorylation in cultured rat hippocampus neurons. A sublethal concentration of Aβ1-42 or Aβ1-40 decreased glutamate-induced CREB phosphorylation, whereas pretreatment with nobiletin reversed the Aβ-induced decrease in CREB phosphorylation. The effects of nobiletin on impairment of learning ability were also examined in chronically Aβ1-40 infused AD model rats using the eight-arm radial maze. In the AD model rats, nobiletin showed protective effects on Aβ1-40-induced impairment of learning ability. These results suggest that nobiletin has the potential for becoming a novel lead compound for drug development for AD.

Original languageEnglish
Pages (from-to)230-234
Number of pages5
JournalNeuroscience Letters
Volume400
Issue number3
DOIs
Publication statusPublished - 2006 Jun 12

Keywords

  • Alzheimer's disease model rats
  • Memory
  • Nobiletin
  • PKA/CREB-dependent signaling pathway

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Nobiletin restoring β-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer's disease model rats'. Together they form a unique fingerprint.

  • Cite this

    Matsuzaki, K., Yamakuni, T., Hashimoto, M., Haque, A. M., Shido, O., Mimaki, Y., Sashida, Y., & Ohizumi, Y. (2006). Nobiletin restoring β-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer's disease model rats. Neuroscience Letters, 400(3), 230-234. https://doi.org/10.1016/j.neulet.2006.02.077