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

It has been found that insulin-like growth factor I (IGF-I) exerts cytoprot ection against A beta amyloid-induced neuronal cell death. Deposits of A be ta 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 pro tein (APP), and we found that IGF-I protected cells from toxicity of FAD-as sociated 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 recep tor (IGF-IR) mediates the protective activity of IGF-I. The antagonizing fu nction of the IGF-I/IGF-IR system against V642I-APP, which is further antag onized by IGFBP-3, provides a molecular clue to the understanding of AD pat hophysiology and to the establishment of potential therapy for AD.