CTF1-51, a truncated carboxyl-terminal fragment of amyloid precursor protein, suppresses the effects of Aβ42-lowering γ-secretase modulators

Haruhiko Watahiki, Sosuke Yagishita, Eugene Futai, Shoichi Ishiura

Research output: Contribution to journalArticle

Abstract

The pathogenesis of Alzheimer's disease (AD) is correlated with the toxicity of amyloid β-peptide (Aβ), especially Aβ42. γ-Secretase modulators (GSMs) are compounds that alter production of Aβ42 without interfering with the physiological function of γ-secretase. Aβ42-lowering GSMs have been studied with the hope of using them as therapeutic or prophylactic drugs for AD. However, the mechanism of action of GSMs is not well defined. We examined the effect of Aβ42-lowering GSMs on model cells producing large amounts of Aβ42: CHO cells expressing CTF1-51, a precursor peptide of Aβ that is mainly cleaved into Aβ42. Our results indicate that the effect of GSM in the model was weak. Thus, we conclude that CTF1-51 cleavage mainly yields Aβ42 and suppresses the effects of some GSMs, a phenomenon that may be related to their mechanism of action.

Original languageEnglish
Pages (from-to)96-99
Number of pages4
JournalNeuroscience Letters
Volume526
Issue number2
DOIs
Publication statusPublished - 2012 Sep 27

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein (APP)
  • Amyloid β-peptide (Aβ)
  • γ-Secretase modulator

ASJC Scopus subject areas

  • Neuroscience(all)

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