Insulin-like growth factor I (IGF-I) protects cells from apoptosis by Alzheimer's V642I mutant amyloid precursor protein through IGF-I receptor in an IGF-binding protein-sensitive manner

Takako Niikura, Yuichi Hashimoto, Takashi Okamoto, Yoichiro Abe, Takashi Yasukawa, Masaoki Kawasumi, Takako Hiraki, Yoshiko Kita, Kenzo Terashita, Keisuke Kouyama, Ikuo Nishimoto

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

It has been found that insulin-like growth factor I (IGF-I) exerts cytoprotection against Aβ amyloid-induced neuronal cell death. Deposits of Aβ amyloid are one of the pathological hallmarks of Alzheimer's disease (AD). Here, we examined whether IGF-I exerts protective activity against cell death induced by a familial AD (FAD)-linked mutant of amyloid precursor protein (APP), and we found that IGF-I protected cells from toxicity of FAD-associated V642I mutant of APP in multiple cell systems. IGFBP-3 blocked this action of IGF-I, but not of des(1-3)IGF-I, which was as active as IGF-I in the presence of IGFBP-3. The data also demonstrated that the IGF-I receptor (IGF-IR) mediates the protective activity of IGF-I. The antagonizing function of the IGF-I/IGF-IR system against V642I-APP, which is further antagonized by IGFBP-3, provides a molecular clue to the understanding of AD pathophysiology and to the establishment of potential therapy for AD.

Original languageEnglish
Pages (from-to)1902-1910
Number of pages9
JournalJournal of Neuroscience
Volume21
Issue number6
DOIs
Publication statusPublished - 2001 Mar 15

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Des(1-3)IGF-I
  • IGF-I
  • IGFBP
  • Neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)

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