TY - JOUR T1 - 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 JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1902 LP - 1910 DO - 10.1523/JNEUROSCI.21-06-01902.2001 VL - 21 IS - 6 AU - Takako Niikura AU - Yuichi Hashimoto AU - Takashi Okamoto AU - Yoichiro Abe AU - Takashi Yasukawa AU - Masaoki Kawasumi AU - Takako Hiraki AU - Yoshiko Kita AU - Kenzo Terashita AU - Keisuke Kouyama AU - Ikuo Nishimoto Y1 - 2001/03/15 UR - http://www.jneurosci.org/content/21/6/1902.abstract N2 - 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. ER -