Reference - Detail
|Author||Niikura T, Hashimoto Y, Okamoto T, Abe Y, Yasukawa T, Kawasumi M, Hiraki T, Kita Y, Terashita K, Kouyama K, Nishimoto I.|
|Title||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.|
It has been found that insulin-like growth factor I (IGF-I) exerts cytoprotection against Abeta amyloid-induced neuronal cell death. Deposits of Abeta 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.
|MeSH||Amino Acid Substitution Amyloid beta-Protein Precursor / genetics Amyloid beta-Protein Precursor / metabolism* Amyloid beta-Protein Precursor / pharmacology Animals Antibodies / pharmacology Apoptosis / drug effects* Cell Line Dose-Response Relationship, Drug Humans Insulin-Like Growth Factor Binding Protein 3 / metabolism Insulin-Like Growth Factor Binding Protein 3 / pharmacology Insulin-Like Growth Factor I / antagonists & inhibitors Insulin-Like Growth Factor I / metabolism* Insulin-Like Growth Factor I / pharmacology Mice Mutagenesis, Site-Directed Peptide Fragments / pharmacology Protein Binding / drug effects Protein Binding / physiology RNA, Messenger / metabolism Receptor, IGF Type 1 / antagonists & inhibitors Receptor, IGF Type 1 / genetics Receptor, IGF Type 1 / metabolism* Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes / cytology T-Lymphocytes / metabolism Transfection|
|DNA material||pco12 EGFR (RDB01276)|