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 Koyama, Ikuo Nishimoto

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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
Publication statusPublished - 2001 Mar 15

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Insulin-Like Growth Factor Binding Proteins
IGF Type 1 Receptor
Mutant Proteins
Insulin-Like Growth Factor I
Amyloid
Apoptosis
Insulin-Like Growth Factor Binding Protein 3
Amyloid beta-Protein Precursor
Alzheimer Disease
Cell Death
Cytoprotection
Amyloid Plaques

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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

In: Journal of Neuroscience, Vol. 21, No. 6, 15.03.2001, p. 1902-1910.

Research output: Contribution to journalArticle

Niikura, T, Hashimoto, Y, Okamoto, T, Abe, Y, Yasukawa, T, Kawasumi, M, Hiraki, T, Kita, Y, Terashita, K, Koyama, K & Nishimoto, I 2001, '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', Journal of Neuroscience, vol. 21, no. 6, pp. 1902-1910.
Niikura, Takako ; Hashimoto, Yuichi ; Okamoto, Takashi ; Abe, Yoichiro ; Yasukawa, Takashi ; Kawasumi, Masaoki ; Hiraki, Takako ; Kita, Yoshiko ; Terashita, Kenzo ; Koyama, Keisuke ; Nishimoto, Ikuo. / 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. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 6. pp. 1902-1910.
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