QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (39) Citing Articles via Google Scholar Google Scholar Articles by Niikura, T. Articles by Nishimoto, I. Search for Related Content PubMed PubMed Citation Articles by Niikura, T. Articles by Nishimoto, I.

 Previous Article  |  Next Article 

The Journal of Neuroscience, March 15, 2001, 21(6):1902-1910

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 Niikura¹, Yuichi Hashimoto¹, Takashi Okamoto², Yoichiro Abe¹, Takashi Yasukawa¹, Masaoki Kawasumi¹, Takako Hiraki¹, Yoshiko Kita¹, Kenzo Terashita¹, Keisuke Kouyama¹, and Ikuo Nishimoto¹

¹ Department of Pharmacology and Neurosciences, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan, and ² RIKEN Brain Science Institute, Hirosawa, Wako-shi, Saitama 351-0198, Japan

It has been found that insulin-like growth factor I (IGF-I) exerts cytoprotection against A amyloid-induced neuronal cell death. Deposits of A 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.

Key words: IGF-I; IGFBP; des(1-3)IGF-I; amyloid precursor protein; Alzheimer's disease; neuroprotection

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/2161902-09$05.00/0

This article has been cited by other articles:

				A. Gomez-Brouchet, D. Pchejetski, L. Brizuela, V. Garcia, M.-F. Altie, M.-L. Maddelein, M.-B. Delisle, and O. Cuvillier Critical Role for Sphingosine Kinase-1 in Regulating Survival of Neuroblastoma Cells Exposed to Amyloid-beta Peptide Mol. Pharmacol., August 1, 2007; 72(2): 341 - 349. [Abstract] [Full Text] [PDF]

				J Svensson, M Diez, J Engel, C Wass, A Tivesten, J-O Jansson, O Isaksson, T Archer, T Hokfelt, and C Ohlsson Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice. J. Endocrinol., June 1, 2006; 189(3): 617 - 627. [Abstract] [Full Text] [PDF]

				V. C. Russo, P. D. Gluckman, E. L. Feldman, and G. A. Werther The Insulin-Like Growth Factor System and Its Pleiotropic Functions in Brain Endocr. Rev., December 1, 2005; 26(7): 916 - 943. [Abstract] [Full Text] [PDF]

				E. Carro, C. Spuch, J. L. Trejo, D. Antequera, and I. Torres-Aleman Choroid Plexus Megalin Is Involved in Neuroprotection by Serum Insulin-Like Growth Factor I J. Neurosci., November 23, 2005; 25(47): 10884 - 10893. [Abstract] [Full Text] [PDF]

				Y. Hashimoto, O. Tsuji, K. Kanekura, S. Aiso, T. Niikura, M. Matsuoka, and I. Nishimoto The Gtx Homeodomain Transcription Factor Exerts Neuroprotection Using Its Homeodomain J. Biol. Chem., April 16, 2004; 279(16): 16767 - 16777. [Abstract] [Full Text] [PDF]

				H. Shan, M. L. Messi, Z. Zheng, Z.-M. Wang, and O. Delbono Preservation of motor neuron Ca2+ channel sensitivity to insulin-like growth factor-1 in brain motor cortex from senescent rat J. Physiol., November 15, 2003; 553(1): 49 - 63. [Abstract] [Full Text] [PDF]

				M. Ikonen, B. Liu, Y. Hashimoto, L. Ma, K.-W. Lee, T. Niikura, I. Nishimoto, and P. Cohen Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis PNAS, October 28, 2003; 100(22): 13042 - 13047. [Abstract] [Full Text] [PDF]

				Y. Hashimoto, T. Niikura, T. Chiba, E. Tsukamoto, H. Kadowaki, H. Nishitoh, Y. Yamagishi, M. Ishizaka, M. Yamada, M. Nawa, et al. The Cytoplasmic Domain of Alzheimer's Amyloid-{beta} Protein Precursor Causes Sustained Apoptosis Signal-Regulating Kinase 1/c-Jun NH2-Terminal Kinase-Mediated Neurotoxic Signal via Dimerization J. Pharmacol. Exp. Ther., September 1, 2003; 306(3): 889 - 902. [Abstract] [Full Text] [PDF]

				E. Marshman, K. A. Green, D. J. Flint, A. White, C. H. Streuli, and M. Westwood Insulin-like growth factor binding protein 5 and apoptosis in mammary epithelial cells J. Cell Sci., February 15, 2003; 116(4): 675 - 682. [Abstract] [Full Text] [PDF]

				D Liolitsa, J Powell, and S Lovestone Genetic variability in the insulin signalling pathway may contribute to the risk of late onset Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, September 1, 2002; 73(3): 261 - 266. [Abstract] [Full Text] [PDF]

				D. Gurwitz, J. Chapman, and A. Weizman Head circumference and incident Alzheimer's disease: Modification by apolipoprotein E Neurology, May 14, 2002; 58(9): 1440 - 1440. [Full Text] [PDF]

				W. Wei, X. Wang, and J. W. Kusiak Signaling Events in Amyloid beta -Peptide-induced Neuronal Death and Insulin-like Growth Factor I Protection J. Biol. Chem., May 10, 2002; 277(20): 17649 - 17656. [Abstract] [Full Text] [PDF]

				Y. Hashimoto, T. Niikura, Y. Ito, H. Sudo, M. Hata, E. Arakawa, Y. Abe, Y. Kita, and I. Nishimoto Detailed Characterization of Neuroprotection by a Rescue Factor Humanin against Various Alzheimer's Disease-Relevant Insults J. Neurosci., December 1, 2001; 21(23): 9235 - 9245. [Abstract] [Full Text] [PDF]

				Y. Hashimoto, T. Niikura, H. Tajima, T. Yasukawa, H. Sudo, Y. Ito, Y. Kita, M. Kawasumi, K. Kouyama, M. Doyu, et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta PNAS, May 22, 2001; 98(11): 6336 - 6341. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help